Monday, November 24, 2008

Researchers Identify Novel Approach For Suppressing Prostate Cancer Development


Researchers at the University of Southern California (USC) have found that inactivating a specific biomarker for aggressive prostate cancer blocks the development of prostate cancer in animal models.

Newswise — Researchers at the University of Southern California (USC) have found that inactivating a specific biomarker for aggressive prostate cancer blocks the development of prostate cancer in animal models.

Researchers say the upcoming study in the Proceedings of the National Academy of Sciences—now available online—may lead to a novel cancer therapy for humans.

“This research has far-reaching implications in a wide range for human cancers,” says Amy Lee, Ph.D., the study’s principal investigator and the associate director for basic research and holder of the Freeman Cosmetics Chair at the USC/Norris Comprehensive Cancer Center, and professor of biochemistry and molecular biology at the Keck School of Medicine of USC. "It is a breakthrough study.”

Prostate cancer is the most common cancer in men and develops through successive stages. The glucose-regulated protein GRP78 has been identified as a crucial entity in the development of prostate cancer by promoting cancer cell proliferation, mediating oncogenic signaling and protecting cancer cells against cell death resulting from the stress of tumor development, Lee explains.

By suppressing GRP78 expression or activity, the USC researchers found that they could block prostate cancer activation and development resulting from the loss of PTEN, a powerful tumor suppressor gene for a number of human cancers.

Researchers spent more than three years monitoring prostate cancer development in animal models that had been genetically engineered to have both the GRP78 and PTEN tumor suppressor genes inactivated. The research was conducted by Yong Fu, a Ph.D. candidate at the Keck School of Medicine of USC and the first author on the study, in collaboration with Ph.D candidates Shiuan Wey, Miao Wang, Risheng Ye and Chun-Peng Liao and Pradip Roy-Burman, M.D., professor of pathology, biochemistry and molecular biology at the Keck School.

Future research should test the role of GRP78 in other types of cancer and isolate drugs that inhibit GRP78, Lee says.

“To our knowledge, this is the first demonstration that inactivation of a specific molecular chaperone from the mouse prostate epithelial cells can potently block prostate cancer development and suppress the activation of AKT, which is a protein kinase that promotes cell proliferation and survival and is a major factor in many types of cancer,” Lee says. “With the recent advances in identifying agents that suppress GRP78 expression, anti-GRP78 therapy may open up an entirely new approach to stop human cancer.”

The study was funded by a grant from the National Cancer Institute that has been awarded to Amy Lee for the past 28 years.

Yong Fu, Shiuan Wey, Miao Wang, Risheng Ye, Chun-Peng Liao, Pradip Roy-Burman, and Amy S. Lee. "Pten null prostate tumorigenesis and AKT activation are blocked by targeted knockout of ER chaperone GRP78/BiP in prostate epithelium." Proceedings of National Academy of Sciences. Nov. 2008.

Friday, October 17, 2008

Interim Phase II Results Support Efficacy of Abiraterone Acetate in Advanced Prostate Cancer Patients

Positive Phase II Data on Cougar Biotechnology's CB7630 Presented at Prostate Cancer Foundation Scientific Retreat

LOS ANGELES, Oct 17, 2008 (BUSINESS WIRE) -- Cougar Biotechnology, Inc. (CGRB) today announced that results from an ongoing Phase II clinical trial of Cougar's investigational drug CB7630 (abiraterone acetate) were presented today at the Prostate Cancer Foundation Scientific Retreat. The Prostate Cancer Foundation Scientific Retreat is currently taking place in Lake Tahoe, Nevada.

The clinical trial of CB7630 was conducted at the University of Texas M.D. Anderson Cancer Center in order to investigate associations between serum and microenvironment (bone marrow) androgen concentrations and response to CB7630. In the trial, CB7630 in combination with prednisone was administered orally, once daily, to patients with castration resistant prostate cancer (CRPC), who had progressive disease despite treatment with LHRH analogues and multiple other therapies. All of the 44 patients who were enrolled in the trial had radiological evidence of metastatic disease with bone metastases. Thirty-eight patients (86%) had at least 10 metastatic bone lesions, 7 patients (16%) had metastases in the liver and 14 patients (32%) had lymph node metastases. Twenty-five (57%) of the 44 patients had received prior treatment with ketoconazole and/or diethylstilbesterol and 38 patients (86%) had received prior treatment with chemotherapy, with 27 patients (61%) having received two or more prior chemotherapy regimens before entering the trial.

In her poster presentation entitled, "Identification of an androgen withdrawal responsive phenotype among patients with castrate resistant prostate cancer (CRPC) treated with abiraterone acetate, a selective CYP17 inhibitor (COU-AA-BMA)," Dr. Eleni Efstathiou from the University of Texas MD Anderson Cancer Center presented data on the 41 evaluable patients treated in the trial. Of the 41 evaluable patients, 21 patients (51%) experienced a confirmed decline in prostate specific antigen (PSA) levels of greater than 50% with a median duration of 6+ months. In addition, 5 patients (12%) experienced PSA declines of greater than 90%. Of the 41 evaluable patients, 24 (59%) experienced an improvement in performance status.
Of the 16 evaluable patients with bone metastases, after 6 months of treatment 4 patients (25%) showed an improvement in their bone scan and 11 patients (69%) showed a stable bone scan. Also, 5 of 5 patients with lymph node metastases showed stable disease after 6 months of treatment with CB7630 and 1 of 2 patients with liver metastases demonstrated a partial radiological response (as measured by the RECIST criteria).

Both serum and bone marrow testosterone levels were measured before and after treatment with CB7630. A decline in both serum and bone marrow testosterone levels to below detectable levels (<10ng/ml.

SOURCE: Cougar Biotechnology, Inc.

Thursday, September 11, 2008

Cancer Stem Cells Isolated: Could Lead To New Drugs To Stop Cancer From Returning

ScienceDaily (Sep. 11, 2008) — After years of working toward this goal, scientists at the OU Cancer Institute have found a way to isolate cancer stem cells in tumors so they can target the cells and kill them, keeping cancer from returning.

A research team led by Courtney Houchen, M.D., and Shrikant Anant, Ph.D., discovered that a particular protein only appears in stem cells. Until now, researchers knew of proteins that appeared in both regular cancer cells and stem cells, but none that just identified a stem cell.

The group has already begun work to use the protein as a target for a new compound that once developed would kill the stem cells and kill the cancer. By targeting the stem cells, scientists and physicians also would be able to stop the cancer from returning.

Houchen and Anant are focusing on adult cancer stem cells because of the major role they play in the start of cancer, the growth of cancer, the spread of cancer and the return of cancer.

Current therapies generally do not target stem cells in tumors. This allows stem cells to wait until after chemotherapy or radiation treatments to begin dividing. Researchers believe these stem cells are often responsible for the return of cancer after treatment. The identification of the stem cell marker enables researchers to develop new therapeutics that can target these cells.

Adult stem cells work as essential building blocks in organs by replenishing dying cells and regenerating damaged tissues. Unlike embryonic stem cells, the use of adult stem cells in research and therapy is not controversial because the production of adult stem cells does not require the destruction of an embryo.

Researchers expect to have initial testing completed to begin the first phase of clinical trials within 5 years led by Russell Postier, M.D. The compound, if successful in human trials, is expected to be available to the public within 10 years.

A quarter of the funding for the cancer research comes from an $800,000 grant from the National Institutes of Health with remaining funds from the University of Oklahoma College of Medicine.

Adapted from materials provided by University of Oklahoma.

Thursday, July 24, 2008

Dramatic new treatment

(From Mata Media)

The news about the groundbreaking treatment for prostate cancer has recieved extensive coverage in the international media. The man behind the new research is Maltese born Dr Johann De Bono. Thomas H. Maugh writes in the Los Angeles Times:

An experimental cancer drug shrank prostate tumors dramatically and more than doubled survival in 70% to 80% of patients with aggressive cancers, British researchers reported Tuesday. Although the study published in the Journal of Clinical Oncology covered only 21 patients, the drug is now being tested in more than 250 men with what appears to be similar results, experts said.

"There is a general sense in the prostate cancer community that this agent is extremely promising and is very likely to have an important role in the management of prostate cancer patients," said Dr. Howard M. Sandler, a radiation oncologist at the University of Michigan who is a spokesman for the American Society of Clinical Oncology."It's pretty safe to say that we are going to have a lot more to offer patients when this drug gets approved," added Dr. Robert Reiter, a urologist at UCLA's Jonsson Comprehensive Cancer Center who was not involved in the research.

Experts expect the new drug, called abiraterone, to be widely available by 2011. It could find use among most of the 28,000 U.S. men diagnosed each year with the most aggressive and almost-always fatal type of prostate cancer.The trial was sponsored by Cougar Biotechnology Inc. of Los Angeles, which holds the patent rights to abiraterone.The drug is also being tested for breast cancer, but no results have been released yet. Key to the excitement is the drug's unusual way of working.

In the new study, Dr. Johann S. de Bono of the institute and his colleagues studied 21 men whose tumors were resistant to chemical castration. The men were given once-daily oral doses of abiraterone. "The drug is spectacularly effective," De Bono said. "The tumors shrink, the pain goes away. Some patients . . . have been on it for up to two years and eight months and are still doing well." Reiter noted that "these guys were at the end stage of disease, the worst stage of cancer, and 70% responded in a clinically meaningful way. That's pretty dramatic . . . and is likely to lead to a major change in therapy." Historically, he added, most such patients die within six months.

Tuesday, July 22, 2008

Magenetic Nanoparticles To Combat Cancer

ScienceDaily (2008-07-22) -- Scientists have developed a potential new treatment against cancer that attaches magnetic nanoparticles to cancer cells, allowing them to be captured and carried out of the body. The treatment has been tested in the laboratory and will now be looked at in survival studies. ...
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"Major breakthrough" in prostate cancer research

United kingdom researchers yesterday annouced what some call the most important breakthrough in prostate cancer treatment in 70 years.

Abiraterone, the new drug being tested, may offer hope for treatment of advanced prostate cancer tumors for up to 80% of men for who treatmnet options were limited.

One physician said while not offering a cure for prostate cancer, this may open the door to making PCa a "treatable disease".

Encouraging news!