Cancer is not just one disease. It is a group of more than 100 different and distinctive diseases. Bringing together data, related to cancer, in an organized manner, is the task of ONCOWIKIA.

Friday, May 20, 2011

Pfizer's Sutent Approved By FDA For Treating Rare Type Of Pancreatic Cancer

The U.S. Food and Drug Administration today approved Sutent (sunitinib) to treat patients with progressive neuroendocrine cancerous tumors located in the pancreas that cannot be removed by surgery or that have spread to other parts of the body (metastatic).
Neuroendocrine tumors found in the pancreas are slow-growing and rare. It is estimated that there are fewer than 1,000 new cases in the United States each year.
This is the second new approval by the FDA to treat patients with this disease; on May 5, the agency approved Afinitor (everolimus).

“FDA believes it is important to provide cancer patients with as many treatment options as possible,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. “The agency is committed to working with companies to bring innovative new therapies to the market and encourages companies to continue exploring additional uses for approved products.”
The safety and effectiveness of Sutent was established in a single study of 171 patients with metastatic (late-stage) or locally advanced (disease that could not be removed with surgery) disease who received Sutent or a placebo (sugar pill). The study was designed to measure the length of time a patient lived before their disease spread or worsened (progression-free survival).
Results from the study demonstrate that Sutent provided benefit to patients by prolonging the median length of time they lived without the cancer spreading or worsening to 10.2 months compared to 5.4 months for patients who received placebo.
In patients treated with Sutent for neuroendocrine pancreatic tumors, the most commonly reported side effects included diarrhea, nausea, vomiting, fatigue, anorexia, high blood pressure, energy loss (asthenia), stomach (abdominal) pain, changes in hair color, inflammation of the mouth (stomatitis), and a decrease in infection-fighting white blood cells (neutropenia).
Sutent is also FDA-approved to treat patients with late-stage kidney cancer (metastatic renal cell carcinoma) and to treat patients with GIST (gastrointestinal stromal tumor), a rare cancer of the stomach, bowel, or esophagus.
Sutent is marketed by New York City-based Pfizer.

Zytiga (abiraterone acetate) Approved For Treating Late-stage Prostate Cancer

The U.S. Food and Drug Administration today approved Zytiga (abiraterone acetate) in combination with prednisone (a steroid) to treat patients with late-stage (metastatic) castration-resistant prostate cancer who have received prior docetaxel (chemotherapy).
In prostate cancer, the male sex hormone testosterone stimulates prostate tumors to grow. Drugs or surgery are used to reduce testosterone production or to block testosterone’s effects. However, sometimes prostate cancer can continue to grow even when testosterone levels are low. Men with these cancers are said to have castration-resistant prostate cancer. 

Zytiga is a pill that targets a protein called cytochrome P450 17A1 (CYP17A1) which plays an important role in the production of testosterone. The drug works by decreasing the production of this hormone that would stimulate cancer cells to continue growing.
The application was reviewed under the FDA’s priority review program, which provides for an expedited six-month review for drugs that may offer major advances in treatment, or provide a treatment when no adequate therapy exists. Zytiga is being approved ahead of the product’s June 20, 2011 regulatory goal date.
“Zytiga prolonged the lives of men with late-stage prostate cancer who had received prior treatments and had few available therapeutic options,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research.
Zytiga’s safety and effectiveness were established in a clinical study of 1,195 patients with late-stage castration-resistant prostate cancer who had received prior treatment with docetaxel chemotherapy. Patients received either Zytiga once daily in combination with prednisone two times a day or a placebo (sugar pill) twice daily in combination with prednisone.
The study was designed to measure overall survival, the length of time from when the treatment started until a patient's death. Patients who received the Zytiga and prednisone combination had a median overall survival of 14.8 months compared to 10.9 months for patients receiving the placebo and prednisone combination.
The most commonly reported side effects in patients receiving Zytiga included joint swelling or discomfort, low levels of potassium in the blood, fluid retention (usually of the legs and feet), muscle discomfort, hot flashes, diarrhea, urinary tract infection, cough, high blood pressure, heartbeat disorders, urinary frequency, increased nighttime urination, upset stomach or indigestion and upper respiratory tract infection.
Zytiga is marketed by Horsham, Pa.-based Centocor Ortho Biotech, Inc.
The press release could be found here.

Digoxin (Lanoxin) A Heart Drug Might Aid Fighting Prostate Cancer

According to a recent study which was published in the journal Cancer Discovery suggests that digoxin (Lanoxin), a drug has long been used to treat heart failure and heart rhythm abnormalities, might help patients with prostate cancer.
The study conducted by Johns Hopkins in a two-part study to explore and locate current drugs on the market for other deceases and conditions could treat prostate cancer. The researchers screened 38 non-chemotherapy drugs to see if they had any effect on cancer. The research found out that Digoxin reduced the growth of prostate cancer cells in the laboratory by 50%

Identification of novel indications for commonly prescribed drugs could accelerate translation of therapies. We investigated whether any clinically used drugs might be useful in treating prostate cancer by coupling an efficient, high-throughput laboratory-based screen and a large prospective cohort study. In stage one, we conducted an  in vitro prostate cancer cell cytotoxicity screen of 3,187 compounds. Digoxin emerged as the leading candidate, given its potency in inhibiting proliferation  in vitro  (the concentration of the drug at which proliferation was inhibited by 50%: mean of 163 nM) and its common use. In stage two, we evaluated the association between the leading candidate drug from stage one and prostate cancer risk in 47,884 men followed up from 1986 through 2006. Regular digoxin users [vs nonusers: relative risk (RR)  = 0.76; 95% confidence interval (CI), 0.61–0.95], especially users for  ≥10 years (RR = 0.54; 95% CI, 0.37–0.79;  P  trend < 0.001), had a lower prostate cancer risk. Digoxin was highly potent in inhibiting prostate cancer cell growth  in vitro,  and its use was associated with a 25% lower prostate cancer risk.

The second part of the study, conducted from 1986 - 2006, they examined the impact of digoxin use in 47,884 men between the ages of 40 and 75 who participated. fter 20 years, some 5,000 cases of prostate cancer had been reported. The digoxin users had a 25% lower risk of prostate cancer than nonusers, and the risk was lower still among men who had used the drug for 10 years or longer.
You can read the complete article over at the Journal Cancer Discovery Research paper.

Monday, May 16, 2011

The anti-inflammatory drug celecoxib (Celebrex) Triggers Liver Cancer Cell Death By Forcing Cancer Cells To Commit Suicide!

 COLUMBUS, Ohio – The anti-inflammatory drug celecoxib, known by the brand name Celebrex, triggers liver cancer cell death by reacting with a protein in a way that makes those cells commit suicide, according to a new study.

Researchers also found that the combination of celecoxib with each of two chemotherapy drugs killed more liver cancer cells in culture, making those combinations more effective than either drug on its own.

"Each chemotherapy drug alone will reduce the growth of cancer cells, but when each single drug is combined with Celebrex, a greater growth suppression effect was observed," said Jiayuh Lin, senior author of the study and an associate professor of pediatrics at Ohio State University. "For clinicians, this research suggests the possibility of a new therapeutic strategy."

Celecoxib has this effect by acting on STAT3, a gene inside liver cancer cells that, when activated, allows those cancer cells to resist the effects of chemotherapy drugs. The researchers determined that the celecoxib molecule binds to STAT3 on so-called "hot spots," effectively blocking its ability to function.

Powerful computing techniques were employed before the researchers ever considered celecoxib as a potential treatment for cancer. Celebrex is a nonsteroidal anti-inflammatory drug, or NSAID, and a Cox-2 inhibitor, meaning it helps control inflammation by inhibiting an enzyme known as cyclooxygenase-2. It is most commonly prescribed to treat the pain of arthritis.

Chenglong Li, an assistant professor of medicinal chemistry and pharmacognosy at Ohio State, has developed computer simulations to identify optimal drug fragment combinations that attach simultaneously to proteins in ways that block the proteins' functions. By searching a database of existing federally approved drugs, he found that celecoxib was structurally similar to a template molecule that he had determined would most effectively bind to STAT3 and inhibit its function.

"Normally, STAT3 is persistently activated in cancer cells. If you have a good molecule that sticks to STAT3, it will prevent its activation," Li said. And when STAT3 is inhibited, cellular survival pathways are blocked that cause the cancer cell to chop itself up and die.

The research appears online and is scheduled for later print publication in the journal Cancer Prevention Research.

The biological portion of the study further defined the role of a pro-inflammatory protein in liver cancer's development. The protein, called interleukin-6, or IL-6, is a cytokine, a chemical messenger that causes inflammation, which can have both beneficial and damaging effects in the body. Previous research by other scientists has shown that high levels of IL-6 in the blood are associated with hepatocellular carcinoma, the most common type of liver cancer.

Lin and colleagues determined that IL-6 initiates a chemical reaction called phosphorylation of STAT3. That reaction activates STAT3 inside liver cancer cells, where STAT3 in turn activates at least three other known genes that allow the cells to resist the effects of chemotherapy.

The scientists treated five different types of hepatocellular carcinoma cells with two different doses of celecoxib for two hours, and followed by giving them IL-6 for 30 minutes. The pre-treatment with the lower dose of celecoxib inhibited IL-6's ability to start the reaction that activates STAT3. The higher dose blocked STAT3 altogether.

The researchers then treated a line of liver cancer cells with celecoxib in combination with two chemotherapy drugs: doxorubicin, which is used to treat breast, ovarian, gastric, thyroid and several other cancers, and sorafenib, which is the only chemotherapy medication approved by the Food and Drug Administration for liver cancer treatment. Its brand name is Nexavar.

With both drugs, the addition of celecoxib treatment reduced the number of viable liver cancer cells by anywhere from approximately 50 percent to more than 90 percent, depending on the doses. The combination of celecoxib and sorafenib also significantly limited the cancer cells' ability to form colonies, a key element of tumor growth and survival after the drug treatment.

"Because liver cancer has a very low five-year survival rate, it is most likely that even sorafenib alone may not be effective to cure the cancer," said Lin, also an investigator in Ohio State's Comprehensive Cancer Center and the Center for Childhood Cancer at Nationwide Children's Hospital. "We hope that using both drugs together could be more effective. Both celecoxib and sorafenib are already approved by the FDA, so we think this combined treatment should be able to be used in the clinic pretty quickly."

The fifth most common cancer in humans, liver cancer remains one of the most difficult to successfully treat. Patients' overall five-year survival rate is about 10 percent, according to the American Cancer Society.

These experiments were conducted in cell cultures. Further testing would be needed to determine celecoxib's effectiveness in human cancers, Lin noted.

And the powerful computational work led by Li, also an investigator in Ohio State's Comprehensive Cancer Center, is likely to lead to the development of new molecules with even more precise structural relationships with the proteins they are designed to block.

Li's method is called Multiple Ligand Simultaneous Docking. In this work, he used computer simulations to identify "hot spots" on the STAT3 protein – tiny pockets to which molecules could most successfully attach to inhibit the protein's activity. He then searched through drug banks containing more than 7,500 existing and experimental medications to find the most suitable molecular fragments that could be pieced together to produce a new molecule shaped in such a way that it would fit into those pockets.

After designing a template molecule that would most effectively bind to STAT3, he compared that template to the 1,400 federally approved drugs already on the market.

"Celecoxib is almost identical to the molecule template. It attaches to STAT3 in three places. We can optimize celecoxib, and that is expected to come soon. But applying our technique to find those pieces and determining that they come from an existing drug makes the discovery process much faster," said Li, a key co-author of the paper and frequent research collaborator with Lin.

Li has termed this approach as in silico (computer-driven) drug repositioning or repurposing.

The discovery that celecoxib can bind to STAT3 also appears to apply to other cancers. Both Lin and Li were key authors on a recent paper that suggested that celecoxib's ability to block STAT3's function might also make it effective as a treatment for rhabdomyosarcoma, the most common soft tissue cancer in children and adolescents. This research was published in the April 15 issue of the journal Biochemical and Biophysical Research Communications.

Contact: Jiayuh Lin
Ohio State University

Co-authors of the liver cancer and rhabdomyosarcoma studies include Yan Liu, Aiguo Liu and Suzanne Reed of the Center for Childhood Cancer at Nationwide Children's Hospital (Aiguo Liu is also affiliated with Tongji Hospital at Huazhong University of Science and Technology in Wuhan, China); and Huameng Li of Ohio State's Division of Medicinal Chemistry and Pharmacognosy and the Biophysics Graduate Program.

This work was supported by grants from the National Institutes of Health and the Department of Defense Congressionally Directed Medical Research Programs.

Contact: Jiayuh Lin, (614) 722-5086; or Chenglong Li, (614) 247-8786;

Written by Emily Caldwell, (614) 292-8310;

Cyber Seminar On Modeling Impact On Cancer Intervention and Surveillance From NCI's CISNET

CISNET is a NCI-sponsored consortium investigating using statistical modeling to improve the understanding of cancer control interventions in prevention, screening, and treatment and their effects on population trends in incidence and mortality.
The models from CISNET could be used in wide variety of needs. They could range from, gaining support for establishment of policies, guidelines, evidence-based cancer control interventions and guide public health research and priorities.
These models could also used to project future trends, and to find the optimal cancer control strategies. CISNET modelers are looking to engage with cancer control planners on local and regional questions amenable to modeling.
So as a part of this engagement, the cyber-seminar for this month will include a panel of the leaders from the five CISNET Coordinating Centers, each with a focus on a specific cancer site (Breast, Colorectal, Esophageal, Lung and Prostate), as well as programmatic leaders from the NCI and CDC.
NCI’s Dr. Eric (Rocky) Feuer, CISNET Director, will provide an overview of the CISNET Consortium..  CISNET modelers will then discuss how modeling tools and data can be used by cancer control practitioners and planners to drive evidence-based interventions and provide current examples of modeling applications.  During the cyber-seminar, CDC ‘s Dr. Laura Seeff, will also announce a new exciting joint NCI-CDC opportunity  for comprehensive cancer control practitioners to work with CISNET researchers in addressing public health problems relevant to their communities through modeling.
Some examples of questions that you could answer using modeling include:
- What is your region’s anticipated need for colonoscopy and if that need was met how would it impact mortality?
- What is the comparative effectiveness of traditional mammogram vs. digital mammogram in your region?
- What would be the impact on lung cancer incidence given specific interventions?
Interested callers will be invited to follow up with the CISNET consortium members to outline possible questions for collaboration (proposal submission form available on Research to Reality).
You can register for the cyber-seminar here.
More information about CISNET

Monday, May 9, 2011

Afinitor (Everolimus) Approved By FDA To Treat Rare Type Of Pancreatic Cancer

FDA approves new treatment for rare type of pancreatic cancer
On Thursday, the U.S. Food and Drug Administration approved Afinitor (everolimus) to treat patients with progressive neuroendocrine tumors located in the pancreas (PNET) that cannot be removed by surgery or that have spread to other parts of the body (metastatic). 
Neuroendocrine tumors found in the pancreas are slow-growing and rare. It is estimated that there are fewer than 1,000 new cases in the United States each year.
“Patients with this cancer have few effective treatment options,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. “Afinitor has demonstrated the ability to slow the growth and spread of neuroendocrine tumors of the pancreas.”
The safety and effectiveness of Afinitor was established a clinical trial in 410 patients with metastatic (late-stage) or locally advanced (disease that could not be removed with surgery) disease. Patients in the study were selected to receive Afinitor or placebo (sugar pill). The trial was designed to measure the length of time a patient lived before their disease spread or worsened (progression-free survival).
In patients treated with Afinitor, the median length of time they lived without the cancer spreading or worsening was 11 months compared with 4.6 months in patients who received placebo. Patients who received placebo were able to receive Afinitor if their disease worsened. 
In patients treated with Afinitor for neuroendocrine pancreatic tumors, the most commonly reported side effects included inflammation of the mouth (stomatitis), rash, diarrhea, fatigue, swelling (edema), stomach (abdominal) pain, nausea, fever, and headache.
Afinitor is also approved to treat patients with kidney cancer (advanced renal cell carcinoma) after they fail treatment with Sutent (sunitinib) or Nexavar (sorafenib); and  patients with subependymal giant cell astrocytoma (a type of brain cancer) associated with tuberous sclerosis (a disease that causes tumors in various parts of the body), who cannot be treated by surgery.  
Afinitor has another trade name, Zortress, and is approved to treat certain adult patients to prevent organ rejection after a kidney transplant. Zortress has a different safety profile in these patients. 
Afinitor is marketed by East Hanover, N.J.-based Novartis.
For more information: