In Brief

From OncoLog, October 2006, Vol. 51, No. 10

In Brief

Overweight Prostate Cancer Patients May Not Fare as Well

Obesity is an independent predictor of whether localized prostate cancer will progress after radiotherapy treatment, say researchers at M. D. Anderson Cancer Center.

In a study reported in the August 1 issue of the journal Cancer, researchers found that moderately and severely obese patients had a 99% greater risk of developing biochemical failure, an early marker of cancer progression, than other patients. The study also reports that obese patients had a 66% increased risk of having a tumor that recurs or becomes metastatic than did non-obese patients.

This finding mirrors results from a parallel study by M. D. Anderson researchers, reported last year in Clinical Cancer Research, that found that a history of weight gain or obesity at the time of diagnosis also played a role in how aggressive prostate cancer may become after surgery.

“Together, these studies confirm that a man’s body mass index (BMI) can be a significant factor in how well he fares after standard treatments for prostate cancer,” said the lead researcher of both studies, Sara Strom, Ph.D., an associate professor in the Department of Epidemiology.

Dr. Strom adds that these findings suggest that obese prostate cancer patients should be followed more closely after treatment. “When patients and their physicians are uncertain about the need for further therapy, our research indicates that a man’s weight should be factored into that decision,” she said.

New Tumor Suppressor Gene Identified

A single gene called BRIT1 plays a pivotal role in launching two DNA damage detection and repair pathways, suggesting that it functions as a tumor suppressor gene, researchers at M. D. Anderson Cancer Center report in the August issue of Cancer Cell.

Defects in BRIT1 seem to be a key pathological alteration in cancer initiation and progression, the authors note, and further understanding of its function may contribute to the development of new treatments for cancer.

“Disruption of BRIT1 function abolishes DNA damage responses and leads to genomic instability,” said senior author Shiaw-Yih Lin, Ph.D., an assistant professor in the Department of Molecular Therapeutics at M. D. Anderson. Genomic instability fuels the initiation, growth, and spread of cancer.

In a series of laboratory experiments, Dr. Lin and colleagues showed that BRIT1 activates two molecular checkpoint pathways. By using small interfering RNA (siRNA) to silence the BRIT1 gene, the scientists shut down both pathways. They then used siRNA to silence the gene in normal human mammary epithelial cells. Inactivation of the gene caused chromosomal aberrations in about a quarter of the treated cells, versus none in the control group.

“We also found that BRIT1 expression is aberrant in several forms of human cancer,” Dr. Lin said. The team found reduced expression of the gene in 35 out of 87 cases of advanced epithelial ovarian cancer. They also found reduced expression in breast and prostate cancer tissue compared with non-cancerous cells.

Drug Turns on Tumor Death Receptors

A clinical trial evaluating a new type of drug that activates death receptors on cancer cells has shown it to be safe and potentially beneficial, reported researchers from M. D. Anderson Cancer Center at the 42nd annual meeting of the American Society of Clinical Oncology.

In an ongoing phase I study, the drug, human Apo2L/TRAIL (Apo2L), has produced only minimal side effects in 58 patients with a variety of advanced cancers, reported Roy Herbst, M.D., Ph.D., professor and chief, Section of Thoracic Medical Oncology. The drug is designed to activate pathways inside tumor cells that lead to the destruction of these cells.

Dr. Herbst also reported that the agent shrunk tumors in one patient with sarcoma and stabilized tumor growth in over half of the patients. He noted, however, that the potential of Apo2L cannot be established yet, especially since the maximum tolerated dose has not yet been determined.

In preclinical studies, Apo2L first caught researchers’ attention when it selectively induced apoptosis in cancer cells while sparing normal cells. It showed activity in animal models of leukemia, non-small cell lung cancer, melanoma, and cancers of the colon, prostate, and breast.

“This is an interesting new class of targeted agents, and Apo2L may well prove to be promising as we study it further,” said Dr. Herbst. He suspects that Apo2L and similar agents being developed will be most effective when used in combination with chemotherapy or radiation. He plans to test a combination of Apo2L and standard chemotherapy.

For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.

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