Possible Therapy Target for Aggressive Cancer Identified

A naturally occurring protein which normally suppresses the growth of cancer cells, causes a rebound effect after a prolonged exposure, UT Southwestern Medical Center researchers have found.

Cancer cells go into overdrive and become even more aggressive and likely to spread, the researchers report.

About Cancer in Women
Cancer is one of the frequently talked about and most feared disease that falls under the genre of lifestyle diseases that have evolved, rather rapidly, in the past two decades.

The mechanism for this reversal is unknown, but UT Southwestern researchers and their colleagues in Indiana suspect that cancerous cells activate a defense mechanism in response to the lethal protein. This mechanism turns on a cascade of cancer-promoting genes.

But clinicians may be able to exploit this rebound for better treatments, said Dr. David Boothman, co-senior author of the study, available online today and appearing in the January issue of The Journal of Clinical Investigation.

"These genetic changes would start prior to metastases, so if we detect them early, we might be able to tailor treatment in anticipation of a more aggressive cancer," said Dr. Boothman, a professor of radiation oncology and pharmacology and associate director of translational research in the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. He also holds the Robert B. and Virginia Payne Professorship in Oncology.

Oral Cancer | Mouth Cancer - Types, Causes, Symptoms, Diagnosis, Treatment & Prevention
Oral cancer is a cancer that develops in any part of the mouth. It is more common in men over 40.

The study was conducted on cells from mice and in samples from women with metastatic breast cancer.

TGF-ÃŸ1 controls many cellular functions, including cell growth, cell proliferation and natural cell death. It also can act to suppress tumors and prevent cancers from spreading.

Pancreatic Cancer - All About the Disease, its Diagnosis and Management
Pancreatic cancer often involves its exocrine part. It grows aggressively, and often detected late. Treatment options include surgery, radiation and chemotherapy.

The researchers, including co-senior collaborator Dr. Lindsey Mayo from the Indiana University School of Medicine, examined a cascade of biochemical reactions in cells exposed to TGF-ÃŸ1. They suspected that prolonged exposure would turn on a particular cancer-causing gene, which in turn, activates other cancer-supporting reactions.

In tissue from women with metastatic breast cancer, 60 percent of the patients showed both TGF-ÃŸ1 action and high levels of the cancer-causing gene.

Cancer Pain - Causes - Effects - Assessment - Treatment - FAQs - Video
Every 1 out of 3 people undergoing cancer treatment experiences pain.

The team also looked at nutlin3, a protein that blocks the action of the cancer-causing gene. They found that nutlin3 blocks the cancer-boosting effects of long-term TGF-ÃŸ1 exposure, preventing metastasis and killing cancer cells. Further research will be needed to determine whether nutlin3 might be worth developing further as an anti-cancer drug, Dr. Boothman said.

In other studies, UT Southwestern researchers found similar effects in cells from colon and non-small cell lung cancers.

Other UT Southwestern researchers involved in the study included Dr. Shinako Araki, postdoctoral fellow in the Simmons Comprehensive Cancer Center; Dr. Xian-Jin Xie, associate professor of clinical sciences and in the Simmons Comprehensive Cancer Center.

The study was supported by grants from the Department of Energy and the National Cancer Institute.

Visit www.utsouthwestern.org/cancercenter to learn more about UT Southwestern''s clinical services in cancer at UT Southwestern.

Source-Newswise
RAS