New Cancer Drug To Be Tested In Wichita

Increasing access to Phase I clinical trials throughout the state is becoming a reality today as officials from The University of Kansas Cancer Center and the Cancer Center of Kansas announced opening Nanotax, a Phase I clinical trial in Wichita.

This is the first Phase I clinical trial discovered, developed and delivered by The University of Kansas Cancer Center, which is a critical component of achieving National Cancer Institute (NCI) designation.

Often the side effects of chemotherapy are as difficult for patients to cope with as the cancer itself. Nanotax, a reformulation of the commonly used chemotherapy drug Paclitaxel, enables the drug to be mixed with water, which significantly reduces its negative side effects.

Nanotax initially opened at The University of Kansas Cancer Center in June 2008. The trial will enroll approximately 21 patients total with advanced peritoneal cancers.

“Our mission is to ensure everyone across the state has access to cutting-edge clinical trials no matter where they live,” said Roy A. Jensen, MD, director of The University of Kansas Cancer Center. “Opening the Phase I clinical trial Nanotax in Wichita moves us closer to fulfilling this mission by giving patients more options close to home.”

Eligible patients can participate in the trial at the Cancer Center of Kansas, under the direction of Shaker Dakhil, MD, FACP, and Thomas Schulz, MD. Drs. Dakhil and Schulz are nationally known oncologists who currently conduct 116 Phase II and Phase III clinical trials.

“The Cancer Center of Kansas has provided patients access to cutting-edge clinical trials for many years,” said Shaker Dakhil, MD, president of the Cancer Center of Kansas. “This Phase I clinical trial will complement the already extraordinary program we have in place and will allow us to offer more options to our patients.”

The trial also complements the Community Clinical Oncology Program (CCOP) grant the Cancer Center of Kansas holds from the National Cancer Institute (NCI), which provides access to Phase II and Phase III clinical trials.

Funding to support the infrastructure needed to conduct a Phase I clinical trial was provided by the Kansas Bioscience Authority (KBA) earlier this year through the Collaborative Cancer Research Initiative program.

The technology that led to the discovery of Nanotax was developed by University of Kansas researchers and was licensed to CritiTech, Inc., a Lawrence-based biotechnology firm, which patented, developed, produced and filed the investigational new drug application with the Food and Drug Administration (FDA). Collaborating with CritiTech and Beckloff and Associates, researchers at The University of Kansas Cancer Center developed the clinical trial.

Demonstrating the ability to translate discoveries made in the lab into new drugs and enrolling patients onto the clinical trial of the new drug helps The University of Kansas Cancer Center meet key criteria needed to apply for NCI designation. Showing the Cancer Center’s ability to conduct translational research while extending the benefits of its research beyond its center is a hallmark of an NCI-designated center.

Source : www.kake.com

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The Truth about Antioxidants and Cancer

You've probably heard about the more common benefits of antioxidants such as its anti-aging effects but do you know that it can also fight one of the deadliest diseases around? Yes, I'm talking about cancer. Read on and find out what it is in the antioxidants that van combat this serious illness and know what foods have high antioxidants content.

A lot has been said about the wonders of antioxidants in our bodies. But are you aware that antioxidants and cancer also have a connection? It's true; antioxidants may save your life by preventing the development of serious illnesses in one's body including one of the most deadly - cancer.

Antioxidants are our bodies' first line of defense in slowing down the destructive action of free radicals, which are found inside the body and in the environment. When they reach high levels in the body, they can be harmful and may cause cancer. Antioxidants have the power to stop free radicals from multiplying and doing severe damage to our bodies.

Research has shown that a high level of antioxidants not only aid in cancer prevention, they also delay the growth of cancer cells already present in the body. Many cancer patients have taken to loading up on antioxidants to somehow slow down the damage cancer brings.

Fruits, vegetables, fish, some meats, nuts and grains and poultry all are packed full of beta-carotene, lutein, Vitamin A, C and E, as well as selenium and lycopene and other vital nutrients. They all work together in your body to get rid of free radicals and restore the cells, skin, tissues and organs back to normal. When you are not fighting against the free radicals, they will multiply in your body. Free radicals live by feeding off vital nutrients in your cells. This leads to cell damage. It is a process going in a vicious circle. When it continues for too long, the free radical damage can lead to cancer.

Antioxidants are the agents that will get rid of these free radicals that have multiplied in our bodies. But you may ask, "How does one develop a high level of free radicals?" While you can also get free radicals from outside pollutants like cigarette smoking, air pollution, and food chemicals, they can also be produced from just doing our day-to-day activities. Walking, sleeping, even the mere process of breathing can form free radicals within our system.

Regardless of whether you are worried about the free radicals in your system causing cancer or you are genetically disposed to get cancer, you should begin to consume a lot more fruits and vegetables, as well as other foods that are packed with them.

There's also another way of increasing your supply of antioxidants in the body without having to consume large amounts of fruits and leafy vegetables. This is by regularly taking a supplement that contains a high level of antioxidants, thereby boosting your body's immune system. A high-quality supplement, a diet that incorporates antioxidant-rich foods, and a healthy lifestyle is your perfect defense against cancer.

Want to know what antioxidant supplement is the best? The supplements that have the most antioxidants are acai supplements! Visit us to discover more about this nutrition-packed berry including health benefits, potential side effects, and acai berry reviews.

by : Travis Van Slooten

Source : www.articlesfactory.com

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New strategy in tumor treatment

A new strategy proposed by researchers at Dartmouth Medical School and Amtek, Hanover, NH may treat tumors that do not respond to conventional treatment. The study, which was published on May 29th in the open access, peer reviewed journal PLoS ONE, uses a combination of two agents to selectively kill tumors while protecting healthy cells.

In previous studies, researchers discovered that a specific enzyme known as methylthioadenosine phosphorylase (MTAP) is missing in 35 to 70 percent of lung, pancreatic and biliary tract cancer, melanoma, glioblastoma, osteosarcoma, soft-tissue sarcoma, mesothelioma, and T-cell acute lymphoblastic leukemia. Although information on the incidence of MTAP-deficiency in breast cancer is still limited, researchers believe it is probably significant.1 Since the discovery of MTAP-negative tumors, there have been several proposals, over the years, to take advantage of the frequent absence of MTAP in so many lethal cancers. None of these proposals, however, has led to successful clinical use.

Dr. Martin Lubin, Professor of Microbiology, Emeritus, and co-author Adam Lubin of Amtek have offered a new approach. They say, “Our strategy consists of two agents. One drug is given that is toxic both to cancer cells and to normal host tissues. A second, but non-toxic, drug is also given, which protects normal tissues from the toxic action of the first agent. This two-drug combination therapy kills tumor cells while normal tissues are well protected.” They go on to state, “Among the drugs used to kill the tumor cells, two — thioguanine and fluorouracil (or its prodrug Xeloda) - are already in clinical use. In general, the dose of these drugs is limited by toxic side effects. However, with our strategy, greatly increased doses might be used and tumors not susceptible to low doses could be attacked successfully at higher doses, without harm to host tissues.”

To assess the selective killing of tumor cells when they were present in excess of normal cells, the researchers designed co-culture experiments in vitro and animal studies are now in progress.

“We hope that successful animal studies will lead to clinical application as soon as possible,” Dr. Lubin said.

Source : www.breakthroughdigest.com

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FDA panel rejects J&J's new cancer drug

Cancer drugs are among the toughest and riskiest medicines to develop, because many of them offer only a small incremental benefit at a steep cost to patients and payers.

That's a lesson that that Johnson & Johnson and partner Zeltia are learning again today, after an FDA advisory panel voted to reject a new drug for ovarian cancer.

The panel said that risks of heart and liver toxicity outweight its ability to keep the disease in check, according to Reuters.

The panel voted 14-1 to recommend that the FDA reject the drug, called Yondelis. The FDA often follows the advisory panel's recommendations.

The panel also pointed out that the 6-week benefit in progression-free survival shown in a pivotal late-stage clinical trial did not justify approval.

Source : blogs.indystar.com

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Resveratrol And Cancer

The "French Paradox" has often bewildered people. It is the conception that the French can indulge in a not very healthy diet, while having a low case of cancer and circulatory diseases. This evidence was hard to comprehend for many as it looks to go
indicate a direct relationship between a high fat diet and disease.

People were curious of the "French Paradox" and, scientists then started to find out the ground for these determinations. The fact that the French typically drink a large total amount of red wine was considered to be one of the reasons for the French not getting cancer and other diseases. Naturally, individuals were keen to ask why this is, because on the surface it appears to be hard to grasp. actually have a good impact on health, due to the fact it has a large amount of the molecule Resveratrol in it.

Resveratrol has beenidentified as having the ability to be vital to improvements made in the way we This is due to it being presented to be an working antioxidant and is as a result capable of stopping and fixing damage from free radicals - which are mismatched electrons that have to the potential to cause disease, harm cells and be accountable for general aging. Resveratrol has the ability to reduce the potency of, as well as aid normal of radiation.

As a result, products designed purposefully to contain a significant amount of Resveratrol are seen as an improvement on other interventions, such as chemotherapy, which kills healthy cells along with cancerous ones. ability to key out between healthy and bad cells and also has the of and remedy of cancer Studies indicates that Resveratrol can provide the creation of advances in conquering and stopping prostate.

However, Resveratrol is most working when it is similar anti-cancer effects. scientists have concluded that when Resveratrol is interacted with green tea it improves its ability to fight against cancer and other diseases caused by long-term inflammation.

Resveratrol is the source of much excitement because scientists regard it as the start of a society which takes measures in order to prevent. In modern society, the way in which we approach the matter of cancer is to respond in a sensitive way – little consideration is given to cancer up until the point we are directly impacted by it. This because until recently, advice on how to prevent has been virtually non-existent.

However, as scientists continue to identify other nutrients integral for long term health including Resveratrol), in possibility the future inhabitants of the earth will have a markedly better knowledge of how to avert diseases like cancer and heart disease. There will be no apologies then.

by : Russell Mcgowan
Source : www.articlealley.com

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Controversial cancer stem cells offer new direction for treatment

In a review in Science, a University of Rochester Medical Center researcher sorts out the controversy and promise around a dangerous subtype of cancer cells, known as cancer stem cells, which seem capable of resisting many modern treatments.

The article proposes that this subpopulation of malignant cells may one day provide an important avenue for controlling cancer, especially if new treatments that target the cancer stem cell are developed and combined with traditional chemotherapy and/or radiation.

“The fact that these concepts are steadily making their way into the clinic is exciting, and suggests that the recent interest in cancer stem cells may yield beneficial outcomes in potentially unexpected ways,” wrote co-authors Craig T. Jordan, Ph.D., professor of Medicine at URMC and director of the James P. Wilmot Cancer Center Translational Research for Hematologic Malignancies program; and Jeffrey Rosen, Ph.D., the C.C. Bell Professor of Molecular and Cellular Biology and Medicine at Baylor College of Medicine.

Cancer stem cells (CSCs) are a hot topic in the scientific community. First identified in 1994 in relation to acute myeloid leukemia, CSCs have now been identified in several solid tumors in mice as well. Scientists who study CSCs believe they have distinct properties from other cancer cells, and may be the first cells to undergo mutations.

Research from the past 10 years suggests that because CSCs may be the root of cancer, they also might provide a new opportunity for a treatment. Jordan and a group of collaborators, for example, are testing a new drug compound based on the feverfew plant that demonstrates great potential in the laboratory for causing leukemia CSCs to self destruct.

Another new approach, the authors said, is the use of chemical screens to search drug libraries for already approved agents that may target CSCs, or make resistant tumor cells more sensitive to chemotherapy and radiation.

Cancer stem cell biologists hypothesize that any treatment that targets the source of origin rather than simply killing all cells, healthy and malignant, would be an improvement over most conventional therapies.

Some scientists, however, are uncertain if CSCs have unique biological properties or any relevance to treatment, the authors noted. What is more likely to fuel cancer, other studies have found, are unfavorable factors in the neighboring cells surrounding the tumor, such as mutated genes, proteins that encourage cell growth, and a poor immune system, for instance.

The most challenging issue facing CSC biologists is that the number and type of cancer stem cells can vary from patient to patient. In some tumor samples, for example, CSCs are rare while in others they constitute a large portion of the tumor mass, the authors said.

To understand why CSCs are so variable, investigators are trying to determine what genes and pathways are responsible for activating cancers that have a poor prognosis, and whether these cancers also have a higher frequency of CSCs.

“Whether the cancer stem cell model is relevant to all cancers or not,” they wrote, “it is clear that we need new approaches to target tumor cells that are resistant to current therapies and give rise to recurrence and treatment failure.”

An unexpected benefit of so much attention on normal stem cells is that it has stimulated research in areas not previously the focus of cancer therapies, Jordan and Rosen said.

For example, pathways known to be important for normal stem cell self-renewal, such as the Wnt, Notch and Hedgehog(Hh) pathways, are now of increased interest due to their potential role in CSCs. The first clinical trial using an agent to block the Notch pathway in combination with chemotherapy for breast cancer has begun.

The authors conclude by spotlighting the pressing need for preclinical models to test appropriate doses and combinations of CSC therapies before they can move into human clinical trials.

Source : www.lifesciencesworld.com

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New Cancer Drug Fights Tumors in Those With BRCA Mutations

A new cancer drug called olaparib worked well in an early clinical trial against breast, ovarian and prostate cancers in individuals who were genetically vulnerable to developing these malignancies.

Women who carry BRCA1 and BRCA2 gene mutations are susceptible to developing breast and ovarian cancer, and among men these mutations are related to an increased risk for prostate cancer, the British researchers noted.

Olaparib works differently than other cancer drugs in that it blocks Poly(ADP-ribose) polymerase (PARP), a protein involved in DNA repair. Healthy cells use PARP to repair themselves, but cancer cells do the same, the scientists explained.

"This is an entirely new class of drugs," said Dr. J. Dirk Iglehart, from the department of surgery at Brigham and Women's Hospital and the department of cancer biology at the Dana-Farber Cancer Institute in Boston, and co-author of an accompanying journal editorial.

When you disable PARP, you prevent the cell from repairing itself, he said, and cancer cells that are deficient in BRCA are much more sensitive to this effect. "When you inhibit PARP, they can't stand it," Iglehart explained.

The report is published online June 24 in the New England Journal of Medicine.

In a phase 1 trial, led by Dr. Johann S. de Bono, from the Institute of Cancer Research at the Royal Marsden NHS Foundation Trust in Sutton, U.K., the scientists treated 60 men and women who were carriers of the BRCA1 or BRCA2 mutations, or had a family history of BRCA-related cancer, with olaparib. All of the patients had either breast, ovarian, prostate, colorectal, melanoma, sarcoma or other cancers.

In this group, there were only a few adverse side effects and they were easily reversed by lowering the dose of the drug, the study noted.

Next, de Bono's team tried the drug on a smaller group of patients, all of whom were confirmed carriers of the BRCA1 or BRCA2 mutation. Those patients received 200 milligrams of olaparib twice a day.

The researchers found that olaparib was absorbed quickly, was eliminated from the body quickly, and had mild side effects. In addition, among people with the BRCA mutations the drug shrunk tumors in breast, ovarian and prostate cancer.

"Olaparib has few of the adverse effects of conventional chemotherapy, inhibits PARP, and has anti-tumor activity in cancer associated with the BRCA1 and BRCA2 mutation," the team concluded.

Iglehart thinks that combining a PARP inhibitor with chemotherapy drugs that damage DNA might make the drug even more effective. "You might then push cancers over the cliff that would be only susceptible to a PARP inhibitor," he said.

In addition, "PARP inhibitors may be used for tumors that Herceptin or tamoxifen are totally incapable of treating," he said. "That's true for ovarian cancer, too. There is nothing to treat that disease."

Two other trials of PARP inhibitors, which were reported on during the American Society of Clinical Oncology annual meeting in June, also found that they were effective in treating breast cancer.

In one trial where PARP inhibitors were combined with standard chemotherapy, there was almost a doubling of survival -- from 5.7 months with chemo alone to 9.2 months when the PARP inhibitor BSI-201 was added, as well as about a 60 percent reduction in the risk of dying from the disease. There were also no additional side effects.

The second PARP inhibitor trial involved 54 women with advanced breast cancer who carried the BRCA mutations. In this trial, 41 percent of patients saw their tumors disappear. There was a slightly lower response rate in the lower-dose group. Mild nausea and fatigue were the most common side effects.

"The drugs are given orally, and it still remains a question as to whether the drugs' benefits will extend beyond this narrow patient population," noted Dr. Eric Weiner, chief of women's cancers at the Dana-Farber Cancer Institute.

"These two studies are very exciting," Dr. Kelly Marcom, a breast oncologist with Duke Comprehensive Cancer Center and director of the Duke Hereditary Cancer Clinic in Durham, N.C., said. "It speaks to a really clever understanding of the biology of the cancer."

Source : www.forbes.com

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Alternative Versus Traditional Cancer Treatments

The reason alternative cancer treatments are not more widely known has little to do with their alleged therapeutic ineffectiveness and far more to do with political control and the therapy marketplace.

Many of the treatments are on the "unproven methods of cancer management" list maintained by the American Cancer Society which is, effectively, a "blacklist".

Medical doctors will know little if anything at all about alternative cancer treatments for a number of reasons.

Medical schools don't teach alternative treatments and medical journals rarely contain articles about alternative treatments. Medical journals are published for the allopathic establishment, and they are mostly financed by advertisements from pharmaceutical companies. Doctors receive a lot of negative information about alternative treatments from the American Medical Association (AMA) and the pharmaceutical industry.

Internet "Quackwatches" and so forth decry alternative therapies even when there is contradictory evidence to their effectiveness plus their state medical boards may fine them heavily, suspend their license to practice or even revoke it.

The American Cancer Society (ACS), the National Cancer Institute (NCI) and other Government cancer bodies will not investigate or promote alternative treatments. If your doctor prescribes treatments that are not FDA approved, he or she can be sued or lose their license. A medical doctor can only prescribe treatments that are Food and Drug Administration (FDA) approved. Their state medical boards may fine them heavily, suspend their license to practice or even revoke it.

The federal government can close them down and confiscate their property and they may lose their right to see patients in hospitals not to mention other doctors/peers openly ridicule and criticize them. It is no wonder your doctor will not know or tell you about alternative cancer treatments, because they could literally lose everything they have and worked for their whole lives.

There are many alternative treatments for cancer that will not provide Big Pharma a single penny of revenue, much less profits. This means these same treatments will not provide the media with a single penny of revenue. Guess which treatments the media pushes?

There is a war going on in medicine today; a war between orthodox medicine and alternative medicine. The war is being fought with money and information. The war is to control what you know, and don't know, about cancer treatments. When a new discovery is made, it comes down to the profitablity. If there is no profit, the treatment is buried.

Find a natural substance that cures something, bury this fact, then fabricate, synthesize, and mutate the key natural substance, then patent the mutation, and make huge profits.

That is why there is "no scientific evidence" for alternative treatments, no one is looking, because they cannot be patented and thus are not profitable enough. The reason there is no official "scientific evidence" for alternative cancer treatments and cancer prevention treatments is that they are not highly profitable to Big Pharma. It is impossible, by law, for a substance to be considered to have "scientific evidence" unless Big Pharma submits it to the FDA, and they will only submit things that are very, very profitable to them.

To the cancer establishment, a cancer patient is a profit center. The actual clinical and scientific evidence does not support the claims of the cancer industry. Conventional cancer treatments are in place as the law of the land because they pay, not heal, the best. Decades of the politics-of-cancer-as-usual have kept you from knowing this, and will continue to do so unless we wake up to their reality.

By : Joni Bell
Source : www.freearticles.co.za

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Discovery could ease cancer pain

A breakthrough could lead to drugs to alleviate the pain experienced by cancer patients.

The biology of cancer pain is different to other types of pain, often rendering analgesic drugs ineffective.

Work by a German team, published in Nature Medicine, shows that blocking a specific type of hormone-like molecule produced by tumours could help.

The team showed that the molecules make nerve endings grow in nearby tissue, causing an acute sensation of pain.

Pain is one of the most debilitating symptoms associated with the many forms of the disease.

It can become excruciating as cancer advances, but tackling it has proved difficult for doctors.

The molecules highlighted by the latest study, by a team at Heidelberg University, were known to play a role in the development of blood cells in the bone marrow.

But this is the first time they have also been shown to have a role in causing pain.

New drugs

The researchers hope their work could lead to new drugs to block this action.

Dr Mark Matfield is scientific adviser to the Association for International Cancer Research, which partly funded the work.

He said: "Identifying one of the ways in which cancer causes pain - in fact, perhaps the main mechanism - is a crucial step towards drugs that could bring relief to cancer sufferers across the world."

Dr Joanna Owens, of the charity Cancer Research UK, said: "It's important that we continue to improve pain relief for people with cancer, and this study reveals an intriguing new avenue to explore.

"What's particularly encouraging is that this research could one day lead to drugs that can block pain locally at the tumour site - which could ultimately lead to more effective pain relief with fewer side effects."

Source : news.bbc.co.uk

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Morphotek(R), Inc. Announces FDA Acceptance for the Treatment of Solid Tu

Morphotek(R), Inc., a subsidiary of Eisai Corporation of North America, announced that the U.S. Food and Drug Administration (FDA) cleared its investigational new drug (IND) application to study MORAb-004 in the treatment of patients with solid tumors. MORAb-004 targets endosialin, a protein expressed on cells associated with tumors and tumor blood vessel cells. The IND became effective 30 days after its initial submission to the FDA by Morphotek.

Some researchers have demonstrated that endosialin, the target of MORAb-004, is necessary for the development of new blood vessels (a process called angiogenesis). New blood vessels are required to provide blood flow to tumors for growth. Endosialin is expressed on pericytes which are cells that surround the smallest blood vessels and are needed for the survival, migration and differentiation of small blood vessels.

"The mechanism of action of MORAb-004, the concept of disturbing the tumor environment, is novel in cancer therapy," said Martin D. Phillips, M.D., Morphotek's Chief Medical Officer. "We are pleased to be carrying out the Phase I study with one of the world's leading health care institutions to focus on treating solid tumors and continue clinical development of this potential new treatment."

MORAb-004, which targets the growth of endosialin-expressing cells in tumor blood vessels, will be used to treat patients with solid tumors. Other anti-angiogenesis drugs target tumor endothelial cells, rather than pericytes. Treatment with MORAb-004 offers an alternative means to suppress tumor angiogenesis and growth.

"MORAb-004 is another unique therapeutic antibody being developed by our company that is believed to inhibit tumor growth via a disease-associated pathway identified and studied by one of our collaborative partners," said Nicholas Nicolaides, President and CEO of Morphotek. "Targeting of pericytes is a novel strategy in the anti-angiogenesis field and we look forward to reporting the results of these studies."

Morphotek obtained exclusive rights to develop and commercialize this antibody worldwide from the Ludwig Institute for Cancer Research (LICR). The endosialin protein as well as a precursor monoclonal antibody specific for endosialin, which is related to MORAb-004, were discovered in Dr. Lloyd Old's laboratory at LICR.

Source : news.prnewswire.com

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Sanofi has winning cancer drug, but short patent

Sanofi-Aventis may have bagged a winning cancer drug when it agreed to buy privately held BiPar Sciences for up to $500 million in April, but a short patent could limit the French group's scope to cash in on sales.

BiPar's BSI-201 has emerged as one of the most promising new products at this year's ASCO cancer conference in Orlando, Florida, with positive mid-stage trial results helping lift Sanofi shares by more than 3 percent on Monday.

But there is a fly in the ointment. A Sanofi spokesman said on Monday that the main U.S. composition patent on the medicine was valid only until 2013, though this could be extended by five years.

In Europe, the patent runs to 2014 and Sanofi will have 10 years data exclusivity after approval.
"These facts probably explain the relatively modest agreed price for the BiPar deal," analysts at Morgan Stanley said in a research note.

They estimate BSI-201 could sell between $1 billion and $4 billion a year to Sanofi's 2016 revenues, with a U.S. launch as possible by late 2010.

On the face of it, that makes the price Sanofi's new chief executive, Chris Viehbacher, paid for BiPar seem a bargain. The problem is the medicine could face generic competition in the world's biggest pharmaceuticals market from 2018.

BSI-201 belongs to a new class of drugs that block a cell repair enzyme known as PARP.

It impressed doctors at the annual meeting of the American Society of Clinical Oncology (ASCO) on Sunday by improving survival by 60 percent compared with chemotherapy alone for women with tough-to-treat "triple negative breast cancer."

Patients with triple negative metastatic breast cancer have tumors that do not express the hormones oestrogen or progesterone, as well as the protein HER-2.

These women, who account for 15 to 20 percent of breast cancer patients, have a very aggressive form of disease and there are currently no treatments other than chemotherapy.

Citigroup analyst Mark Dainty said the data for BSI-201 was significantly better than the results with Roche's Avastin in triple negative patients and the new drug could put 20 to 25 percent of Avastin sales forecasts at risk.

Citi currently forecasts 2011 Avastin breast cancer sales at 1.7 billion Swiss francs ($1.6 billion) and losing 20 percent of this would slice some 2 percent off Roche's 2011 earnings per shares.

AstraZeneca also has an experimental PARP inhibitor called olaparib that is further behind in development.

Source : www.reuters.com

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Bayer Announces New Data on Novel Anti-cancer Compound BAY 73-4506

Bayer today announced results from Phase I and II trials of BAY 73-4506, a potent oral multi-kinase inhibitor currently being studied in multiple tumor types. These data were presented at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO).

"Bayer is committed to discovering new cancer-fighting therapies," said Kemal Malik, MD, Chief Medical Officer and Head of Global Development at Bayer HealthCare. "We are encouraged by these Phase I and II data being presented on BAY 73-4506. These data will help further determine our next steps as we move forward with a comprehensive Phase III clinical development program in various tumor types for this new drug candidate."

Preliminary data from the Phase II, open-label study in renal cell carcinoma (RCC) demonstrated a 27 percent partial response (PR) rate according to the Response Evaluation Criteria in Solid Tumors (RECIST) and a disease control rate of 79 percent. The most common drug-related adverse events were hand-foot skin reaction (HFSR), fatigue, hypertension, mucositis, dysphonia, rash, diarrhea, and anorexia. The Phase II study enrolled 49 previously untreated patients with predominantly clear cell RCC. BAY 73-4506 (160 mg) was administered once daily on a three weeks on/one week off schedule. The primary endpoint was to evaluate response rate according to RECIST.

"We are encouraged by these data of BAY 73-4506," said lead investigator Professor Tim Eisen, F.R.C.P., PhD, of Addenbrooke's Hospital at the University of Cambridge, UK. "These data provide a rationale to move into a Phase III trial in one of the multiple tumor types that may be responsive to BAY 73-4506."

Additional data presented on BAY 73-4506 include a Phase I study of patients with advanced refractory colorectal carcinoma (CRC). The data were presented by lead investigator Dirk Strumberg, MD, Department of Hematology and Medical Oncology, Marienhospital Herne, University Medical School of Bochum, Germany.

Data from the Phase I dose-finding study in CRC showed BAY 73-4506, dosed at 160 mg daily, using a treatment schedule of 21 days on/7 days off, was feasible in patients with advanced refractory CRC. Disease control rate (PR + SD) was 74 percent in evaluable patients. The most common drug-related adverse events were hand-foot skin reaction (HFSR), fatigue, hoarseness, mucositis, diarrhea, anorexia and hypertension. Data presented are based on 38 patients with actively progressing CRC enrolled in a Phase I study. Patients were treated with BAY 73-4506 at doses of 60 mg, 120 mg, 160 mg, and 220 mg once daily.

About BAY 73-4506 (DAST-Inhibitor)

BAY 73-4506 is a dual targeted VEGFR2-TIE2 anti-angiogenic oral tyrosine kinase inhibitor (TKI) with a kinase inhibition profile targeting angiogenic, stromal and oncogenic receptor tyrosine kinases (TK). In preclinical studies, BAY 73-4506 has been shown to inhibit tumor growth by hitting targets along a spectrum of angiogenic pathways, including VEGFR and TIE2. BAY 73-4506 has also been shown in preclinical studies to prevent the proliferation of tumor cell lines while promoting apoptosis (cell death) by directly targeting several oncogenic TK receptors. The clinical significance of these studies is not known and warrant further investigation in a broad spectrum of tumors.

About Bayer HealthCare Pharmaceuticals Inc.

Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals unit of Bayer HealthCare LLC, a subsidiary of Bayer Corporation. One of the world's leading, innovative companies in the healthcare and medical products industry, Bayer HealthCare combines the global activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. In the U.S., Bayer HealthCare Pharmaceuticals comprises the following business units: Diagnostic Imaging, General Medicine, Specialty Medicine and Women's Healthcare. The company's aim is to provide products that will improve human health worldwide by diagnosing, preventing and treating diseases.

Source : news.prnewswire.com

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Novartis, Roche unveil promising cancer drugs data

Swiss drugmaker Novartis AG said late stage data showed its Sandostatin LAR drug helped fight tumuors of the mid-gut, while other drugs showed benefits for treating advanced melanoma.

Novartis' rival Roche Holding AG also said on Thursday a new drug helped shrink the tumours of 25 percent of women with HER2-positive breast cancer, according to data from a mid-stage clinical trial.

Cancer drugs are seen as a key growth area for pharmaceutical makers like the two Swiss companies, which along with many others are presenting data on cancer drugs at an American Society of Clinical Oncology (ASCO) meeting.

Novartis said a Phase III study showed Sandostatin LAR more than doubled time without tumour growth and reduced the risk of disease progression by 67 percent.

It also said mid stage data on two of its drugs showed potential as treatments for advanced melanoma. Favourable results from a study into the drug Glivec mean the study will continue to a second expanded stage of enrolment.

The Swiss company also presented preliminary results which showed that 72 percent of melanoma patients treated with Afinitor combined with Roche's Avastin experienced a clinical benefit.

Afinitor, one of Novartis' most important new drugs, also helped patients with advanced liver cancer in an early stage trial.

Data from a mid stage trial of the new treatment from Roche, a combination of its Herceptin and chemotherapy known as trastuzumab-DM1, showed about 35 percent of a total 112 patients had their tumours shrink, or their disease stabilise for at least six months.

Source : www.reuters.com

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The Vulnerable Cancer Cell: New Studies Reveal Broad, Hidden Network That Lets Tumors Thrive

Howard Hughes Medical Institute researchers have identified many potential new drug targets for cancers long deemed “untouchable” due to the type of genetic mutation they contain. These studies are beginning to reveal new ways of attacking cancer by targeting a largely hidden network of normal genes that cancer cells rely on for survival.

Independent research teams led by Howard Hughes Medical Institute (HHMI) investigators D. Gary Gilliland of Brigham and Women’s Hospital (now senior vice president at Merck Research Laboratories) and Stephen J. Elledge at Harvard Medical School, used RNA interference (RNAi) technology to identify a host of genes that cancer cells depend on for survival. The researchers studied cells with mutations in KRAS, the most commonly mutated gene in human cancers.

KRAS, which was discovered nearly 30 years ago, is mutated in 30 percent of human tumors, including 90 percent of pancreatic cancers, 50 percent of colon cancers, and 30 percent of non-small cell lung cancers.

“Efforts to develop drugs that inhibit oncogenic RAS proteins have been largely unsuccessful, despite the fact that RAS gene family members are mutated in about 30 percent of human tumors,” said Gilliland, who directs the oncology program at Merck.

More than 18 months ago, Elledge and Gilliland decided to see if they could use the powerful RNAi technology to seek out genes that KRAS-mutant cancer cells need for survival. Their efforts, culminating in two reports in the May 29, 2009 issue of the journal Cell, have led to the identification of potentially promising drug targets: serine/threonine kinase 33 (STK33) and polo-like kinase 1 (PLK-1), as well as a host of other proteins.

“These targets represent a potential Achilles heel for tumors,” said Gilliland. “In the case of STK33, it is absolutely required for survival of cancer cells. Normal cells don’t require it.”

“The translational implications of both reports are important and immediate,” wrote Charles L. Sawyers, an HHMI investigator at Memorial Sloan-Kettering Cancer Center. Sawyers discussed the implications of the research in a preview article published in the same issue of Cell.

Sawyers points to the identification of the two kinases as validation of the approaches taken by Elledge and Gilliland. With the dramatic clinical success of cancer drugs, such as Gleevec and dasatinib, which target rogue kinases, Sawyers says any screen that turns up new kinases is worthy of further investigation.

“The new mantra, quite simply, is that cancers bearing oncogenic mutations in a kinase are dependent on that kinase for growth and survival,” writes Sawyers in Cell. “With rare exception, patients with such tumors have derived significant benefit (that is, their tumors shrink) when treated with an inhibitor of that mutant kinase. The probability of success in such patients is so high that drug discovery programs can (and should) be launched when a new kinase mutation is discovered in a subset of human cancers.”

“Hopefully drugs that target non-mutant, but synthetic lethal kinases will be similarly effective,” Sawyers added.

The concept of synthetic lethality – which is part of the intellectual framework of these two studies -- has its roots in yeast genetics. Synthetic lethality is defined as a genetic interaction where the combination of mutations in two or more genes leads to cell death. For example, two different strains of yeast may each harbor a mutation that is not lethal on its own. But when both mutations are combined in a single strain of yeast, death occurs – hence the name, synthetic lethality. “Synthetic lethality is actually co-lethality,” said Elledge.

During the last few years cancer researchers have become increasingly interested in developing synthetic lethality screens as a tool for uncovering genetic dependencies in cancer cells. The rationale behind the strategy is as follows: A mutated cancer-causing gene, or oncogene, causes a cell to grow abnormally. That abnormal growth can lead to the development of a tumor. But oncogenes do not cause cancer by themselves – they depend on the activity of other genes. These genes are considered “dependents,” in the sense that the cancer cell’s survival also depends on the activity of the oncogenes and its dependent genes. Many of these so-called dependent genes are not mutated in cancer cells, but they contribute to abnormal cell growth and cancer. By using RNAi to knock down the expression of individual genes in cells bearing mutations in an oncogene, such as KRAS, researchers can see which gene knock-downs affect cancer cells’ viability. Gene dependencies are uncovered in cancer cells that fail to thrive.

Until recently, however, researchers simply did not have the tools to undertake a large-scale, systematic analysis to uncover genetic dependencies in mammalian cells. The discovery of RNAi a little more than a decade ago is making it possible to do genetics in mammalian cells. The cellular machinery involved in RNAi first identifies short segments of suspicious-looking RNA, and then destroys all identical copies of that RNA. The result: None of the protein that the RNA encodes for gets made.

While the natural function of RNAi is to prevent viruses from replicating inside cells and to control endogenous gene expression, scientists discovered they could exploit the process to squelch individual gene products. To do so, they introduce a short segment of RNA that looks like one of the cell's normal genes. The RNA interference machinery grinds into action and shuts down production of the protein made from that gene.

Gilliland’s team, which included first authors, Claudia Scholl and Stefan Fröhling, as well as HHMI investigator Tyler Jacks at MIT, began their studies about two years ago. The team’s interest in leukemias informed their decision to focus on using short hairpin RNAs (shRNAs) -- single strands of RNA that fold back on themselves -- to selectively knock down the activity of serine/threonine kinases and tyrosine kinases. In recent years, kinase inhibitors have emerged as highly successful therapy for a subset of leukemias.

“We were looking at genes that we thought we could target easily with drugs,” Gilliland said. “We looked for genes that when knocked down would confer lethality to cells that were KRAS-mutant, but not KRAS-wild-type.” This approach is a particularly attractive concept in cancer research because normal cells don’t have the same dependencies on these genes. “If you find a vulnerability conferred by another gene, you should, in theory, have a great therapeutic window because you’re not going to affect normal cells,” he said.

Gilliland’s group began a collaboration with William C. Hahn at the RNAi Consortium at the Broad Institute to use the Broad’s automated RNAi screening technology to assess about 5,000 shRNAs targeting about 1,000 human genes in a panel of eight human cancer cell lines. The shRNAs were carried in lentiviral vectors, which the researchers used to infect four cell lines carrying KRAS mutations and four lines carrying KRAS-wild-type genes.

At the top of the “hits” identified in the screen was the serine/threonine kinase, STK33, which Gilliland describes as a “totally new gene” in cancer research circles. “There are a couple of older papers describing STK33’s genetic localization and exon structure, but otherwise nothing else is known about it.”

That’s about to change as Gilliland and his team begin to explore why STK33 represents a liability for KRAS-mutant cancer cells. Evidence presented in Cell shows that STK33 is not a part of the RAS signaling pathway, nor is it mutated in human cancer cell lines that were tested. Gilliland said his group’s experiments indicate that STK33 is involved in induction of the cell death pathway in cancer cells. “We don’t have all the answers yet, but STK33 is selectively required for the survival and proliferation of mutant KRAS-dependent cancer cells,” Gilliland said.

In the experiments reported in Cell, Elledge and his colleagues used an RNAi technique developed by Elledge and HHMI investigator Greg Hannon at Cold Spring Harbor Laboratory. “Overall, we were asking very simple questions: What do RAS cells need to survive? And is it different from what normal cells need to survive?” said Elledge.

Elledge’s team generated about 75,000 bits of short hairpin RNAs that can be inserted into retroviruses. When the altered retroviruses infected either normal cells or cells that differed by only a single mutation in KRAS, the shRNA bound to corresponding stretches of RNA in the cells, and prevented their translation into proteins.

If the shRNA knocked down production of a protein essential to keeping the cells alive, then the abundance of that particular shRNA quickly diminished as cells died. The researchers could track the identity of the shRNA – and its corresponding gene – by using a “barcoding” method to track the diverse pool of short hairpin RNAs in parallel. In the barcoding method, every short hairpin RNA that is made carries a unique genetic tag. This tag lets the researchers track the effect of thousands of the RNAs in a single pool of cells in a single lab dish. “These are experiments a single researcher can perform in their own lab without the need for complex robotic platforms,” said Elledge.

By tracking the abundance of each shRNA from the total pool and comparing cancer cells to cells from normal tissues, Elledge and his colleague Ji Luo identified many genes that KRAS is dependent on. In this manner, they were able to do a genome-wide survey, uncovering many new potential drug targets, including PLK-1, STK33, and a number of proteins involved in mitosis. “It will take some time to figure this out, but RAS is clearly having some effect on an important part of mitosis,” said Elledge. “Regardless of that mechanism, it provides a vulnerability that we can attack. And fortunately there are a lot of drugs already available that have anti-mitotic properties – and we showed that some of those drugs are more toxic to the RAS cells.”

Furthermore, Elledge’s group found that the expression levels of some of the genes on their “hit” list correlated with patient survival. “This argues that they really do have an important role in the clinical outcomes observed in cancer patients,” said Elledge.

Sawyers thinks these two studies are an important proof-of-concept, but much more work will be needed to identify all the underlying vulnerabilities of cancer cells. “The ultimate validation of the synthetic lethal screening strategies will be evidence that patients KRAS-mutant tumors benefit from treatment with STK33 or PLK1 inhibitors,” Sawyers said. “Unfortunately, we won’t have that answer for many years.”

Source : www.sciencedaily.com

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New tool for next-generation cancer treatments using nanodiamonds

A research team at Northwestern University has demonstrated a tool that can precisely deliver tiny doses of drug-carrying nanomaterials to individual cells.

The tool, called the Nanofountain Probe, functions in two different ways: in one mode, the probe acts like a fountain pen, wherein drug-coated nanodiamonds serve as the ink, allowing researchers to create devices by 'writing' with it. The second mode functions as a single-cell syringe, permitting direct injection of biomolecules or chemicals into individual cells.

The research was led by Horacio Espinosa, professor of mechanical engineering, and Dean Ho, assistant professor of mechanical and biomedical engineering, both at the McCormick School of Engineering and Applied Science at Northwestern. Their results were recently published online in the scientific journal Small.

The probe could be used both as a research tool in the development of next-generation cancer treatments and as a nanomanufacturing tool to build the implantable drug delivery devices that will apply these treatments. The potential of nanomaterials to revolutionize drug delivery is emergent in early trials, which show their ability to moderate the release of highly toxic chemotherapy drugs and other therapeutics. This provides a platform for drug-delivery schemes with reduced side effects and improved targeting.

"This is an exciting development that complements our previous demonstrations of direct patterning of DNA, proteins and nanoparticles," says Espinosa.

Using the Nanofountain Probe, the group injected tiny doses of nanodiamonds into both healthy and cancerous cells. This technique will help cancer researchers investigate the efficacy of new drug-nanomaterial systems as they become available.

The group also used the same Nanofountain Probes to pattern dot arrays of drug-coated nanodiamonds directly on glass substrates. The production of these dot arrays, with dots that can be made smaller than 100 nanometers in diameter, provides the proof of concept by which to manufacture devices that will deliver these nanomaterials within the body.


The work addresses two major challenges in the development and clinical application of nanomaterial-mediated drug-delivery schemes: dosage control and high spatial resolution.

In fundamental research and development, biologists are typically constrained to studying the effects of a drug on an entire cell population because it is difficult to deliver them to a single cell. To address this issue, the team used the Nanofountain Probe to target and inject single cells with a dose of nanodiamonds.

"This allows us to deliver a precise dose to one cell and observe its response relative to its neighbors," Ho says. "This will allow us to investigate the ultimate efficacy of novel treatment strategies via a spectrum of internalization mechanisms."

Beyond the broad research focused on developing these drug-delivery schemes, manufacturing devices to execute the delivery will require the ability to precisely place doses of drug-coated nanomaterials. Ho and colleagues previously developed a polymer patch that could be used to deliver chemotherapy drugs locally to sites where cancerous tumors have been removed. This patch is embedded with a layer of drug-coated nanodiamonds, which moderate the release of the drug. The patch is capable of controlled and sustained low levels of release over a period of months, reducing the need for chemotherapy following the removal of a tumor.

"An attractive enhancement will be to use the Nanofountain Probe to replace the continuous drug-nanodiamond films currently used in these devices with patterned arrays composed of multiple drugs," Ho says. "This allows high-fidelity spatial tuning of dosing in intelligent devices for comprehensive treatment."

"One of the most significant aspects of this work is the Nanofountain Probe's ability to deliver nanomaterials coated with a broad range of drugs and other biological agents," Espinosa says. "The injection technique is currently being explored for delivery of a wide variety of bio-agents, including DNA, viruses and other therapeutically relevant materials."

Nanodiamonds have also proven effective in seeding the growth of diamond thin films. These diamond films have exciting applications in next-generation nanoelectronics. Here again, the ability to pattern nanodiamonds with sub-100-nanometer resolution provides inroads to realizing these devices on a mass scale. The resolution in nanodiamond patterning demonstrated by the Nanofountain Probe represents an improvement of three orders of magnitude over other reported direct-write schemes of nanodiamond patterning.

Source : www.physorg.com

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New warnings for Tarceva cancer drug-U.S. FDA

New warnings have been added to Genentech Inc and OSI Pharmaceutical Inc's (OSIP.O) cancer drug Tarceva about serious complications such as skin reactions and holes in the digestive tract, U.S. health regulators said on Friday.

In some cases patients have died, the U.S. Food and Drug Administration said.

The FDA said that some of the problems suggest larger possible disorders such as Stevens-Johnson syndrome or toxic epidermal necrolysis.

Genentech is a unit of Roche Holding AG (ROG.VX). (Reporting by Susan Heavey).

Source : uk.reuters.com

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New Drug To Target Tumor Cells And Blood Vessels

Researchers at the University of Southern California have identified a new drug compound that appears to target tumor cells and surrounding blood vessels without the negative side effects typically associated with Cox-2 inhibitors.

The compound 2.5-dimethyl-celecoxib (DMC) appears to have a strong anti-tumor effect while also attacking the vasculature that provides the blood supply necessary for tumor growth, according to data presented at the AACR 100th Annual Meeting 2009. The findings were presented on April 19.

"If left behind, the blood vessels within the tumor will help the tumor cells to survive and re-grow," says Florence M. Hofman, Ph.D., professor of pathology at the Keck School of Medicine of USC. "We believe that DMC will be particularly useful for treating brain tumors such as gliomas, which are highly vascular. It also appears very promising for long-term treatment because it does not have the negative cardiovascular effects associated with Cox-2 inhibitors."

Cox-2 inhibitors are most commonly used as anti-inflammatory drugs and have been shown to be effective in treating certain kinds of cancer. However, long-term use has also been associated with increased risk of heart attack and stroke, Hofman explains. DMC, however, retains anti-tumor activity without inhibition of Cox-2 and the associated increased risk of cardiovascular complications.

Hofman and colleagues from the Keck School of Medicine tested the effectiveness of the DMC compound by isolating endothelial cells—the cells that line the interior surface of blood vessels—from human nonmalignant brain and glioma tissues and treating them with DMC.

They found that the drug was cytotoxic to tumor-associated endothelial cells and suppressed cell proliferation and migration without apparent toxic effects to normal tissues. Drug therapy in animal studies also showed smaller tumors and fewer blood vessels in the tumors, with a 35 to 40 percent reduction in blood vessel density.

"While our research focused on brain tumors, we believe this drug may work in a number of different tumors that are dependent on blood vessels," Hofman says. "Further research will help us to understand its full potential."

The research was funded by the L.K. Whittier Foundation through the USC Norris Comprehensive Cancer Center.

Reference: Jenilyn J. Virrey, Adel Kardosh, Encouse Golden, Stan Louie, Nicos Petasis, Axel H. Schönthal, Thomas C. Chen, and Florence M. Hofman. "2, 5-Dimethyl-Celecoxib Exerts Antiangiogenic Effects on the Tumor Vasculature."

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Pathway of dealiest cancers blocked by potential new drug

Scientists from Cancer Research Technology Ltd (CRT) presented new findings at the 2009 AACR Meeting, Denver, showing that a potent and selective inhibitor of protein kinase D called CRT0066101, inhibits the growth of pancreatic tumours.

The research - presented by CRT’s Dr Christopher Ireson - was a collaborative effort between scientists at CRT’s discovery laboratories and the University of Texas MD Anderson Cancer Center. These results show for the first time that an inhibitor of PKD can slow the growth of tumours in pancreatic cancer models. In addition, experiments carried out by CRT have shown that CRT0066101 is also effective at inhibiting the growth of tumours in a lung cancer model. The scientists believe that the drug has the potential to treat other cancers too.

PKD is a relatively newly identified family of serine/threonine kinases comprising PKD1, PKD2 and PKD3. The potential of PKD as a new drug target was discovered by Enrique Rozengurt, Doreen Cantrell and Peter Parker and funded by Cancer Research UK. Following this discovery, an intensive drug discovery effort led by CRT’s Head of Medicinal Chemistry, Dr Tony Raynham, cumulated in the identification of CRT0066101 as a lead candidate for pre-clinical studies. Since then, PKD has been identified as playing a central role in the development of a number of cancers. In addition to its role in the growth of tumour cells, PKD has also been shown to play a pivotal role in cell survival and angiogenesis - a process by which tumours form new blood vessels - which is central to tumour growth and spread.

CRT’s discovery laboratories director Dr Hamish Ryder said: “We focused on pancreatic and lung cancer tumours because they represent cancers with a significant unmet medical need. “The CRT model of combining promising basic science with the capability of the industrially-focus Discovery Laboratories gives us a unique opportunity to rapidly develop potential new molecules to novel targets, and through partnering with industry, explore the potential to see if one day it might help treat cancer patients in the future”.

Dr Sushovan Guha who leads the laboratory at MD Anderson Cancer Center, said: “We are very optimistic about CRT0066101’s pharmacological potential. We believe this is the first orally administered small-molecule inhibitor of PKD with significant biological efficacy in pre-clinical animal models of pancreatic cancer. My conviction is that we will show the drug can also prevent the proliferation of cancer cells by blocking their supply of blood - through neo-angiogenesis. This would mean it offers a double action treatment but this needs to be proved through further work.”

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New drug agent knocks out multiple enzymes in cancer pathway

A team of 24 researchers from the U.S., Europe, Taiwan and Japan and led by University of Illinois scientists has engineered a new anti-cancer agent that is about 200 times more active in killing tumor cells than similar drugs used in recent clinical trials.

The study appears this week in the Journal of the American Chemical Society.

The new agent belongs to a class of drugs called bisphosphonates. These compounds were originally developed to treat osteoporosis and other bone diseases, but were recently found to also have potent anti-cancer and immune boosting properties.

Drug developers have tried for years to design drugs to inhibit cell survival pathways in tumor cells, focusing on a protein called Ras since nearly a third of all human cancers involve a mutation in the Ras gene that causes cell signaling to go awry. These efforts have met with limited success.

Bisphosphonates act on other enzymes, called FPPS and GGPPS, which are upstream of Ras in the cell survival pathway. Inhibiting these enzymes appears to be a more effective strategy for killing cancer cells.

When used in combination with hormone therapy in a recent clinical trial, the bisphosphonate drug zoledronate significantly reduced the recurrence of breast cancer in premenopausal women with estrogen-receptor-positive breast cancer. Similar results were reported previously for hormone-refractory prostate cancer.

But zoledronate quickly binds to bone, reducing its efficacy in other tissues.

"We're trying to develop bisphosphonates that will be very active but won't bind to the bone, because if they bind to the bone they're not going to go to breast, lung or other tissues," said University of Illinois chemistry professor Eric Oldfield, who led the new study.

Oldfield's team also wanted to design a compound that would inhibit multiple enzymes in the tumor cell survival pathway, rather than just one, an approach analogous to the use of multi-kinase inhibitors in cancer therapy.

Andrew Wang, of Academia Sinica, Taipei, and Illinois chemist Rong Cao began by producing crystallographic structures of the target enzymes and drug candidates, allowing the researchers to identify those features that would enhance the drugs' ability to bind to the enzymes. Using this and other chemical data, Illinois chemistry department research scientist Yonghui Zhang engineered new bisphosphonate compounds that bound tightly to multiple enzyme targets, but not to bone.

One of the new compounds, called BPH-715, proved to be especially potent in cell culture and effectively inhibited tumor cell growth and invasiveness.

Tadahiko Kubo, of Hiroshima University, then found that BPH-715 also killed tumor cells in mice. And Socrates Papapoulos, of Leiden University, the Netherlands, showed that the compound had a very low chemical affinity for bone.

In humans, compounds like BPH-715 and zoledronate have an added benefit in fighting cancer: They spur the proliferation of immune cells called gamma delta T-cells, which aid in killing tumor cells.

"The new drugs are about 200 times more effective than the drugs used in recent clinical trials at killing tumor cells and in activating gamma delta T-cells to kill tumor cells," Oldfield said. "They also prevent tumor progression in mice much better than do existing bisphosphonate molecules."

Source : www.eurekalert.org

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Cancer Drug May Offer New Hope for Lupus Patients

The cancer drug Rituxan may offer the first new treatment approved for lupus in 50 years, suggests a small study by U.K. researchers at Imperial College London.

The 22-month study included 20 people with lupus nephritis, a severe kidney disorder caused by the disease lupus. After treatment with Rituxan, 60 percent showed significant signs of improvement, the researchers found. But the drug was not effective in people of African ancestry or in those with very low levels of albumin protein in their blood.

Rituxan targets hyperactive B cells, which contribute to kidney inflammation in people with lupus. If these study results can be repeated in larger trials, Rituxan might be approved to treat lupus, the researchers said.

"This is very welcome news to the 40 percent of lupus patients who are suffering with kidney involvement in their battle with systemic lupus erythematosus, an autoimmune disease, and who until now had very little hope of a breakthrough for lupus nephritis," Virginia T. Ladd, president and executive director of the American Autoimmune Related Diseases Association, said in an association news release.

People with lupus experience a wide range of problems, including muscle pain, extreme fatigue and inflammation of the joints, skin, major organs and central nervous system.

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