Breast Cancer Stem Cells May Resist Radiation Treatment
The population of breast cancer cells that gives rise to a tumor may be relatively resistant to radiotherapy and may even increase when given multiple treatments of radiation, a new study shows.
In the last several years, researchers have discovered a small population of so-called cancer-initiating cells (also called cancer stem cells) in several cancers. These cells can self-renew and maintain the growth of a tumor, whereas its daughter cells cannot. Scientists are studying the properties of cancer-initiating cells because the destruction of these cells is likely necessary for the successful treatment of a cancer.
To test the response of breast cancer-initiating cells to radiation treatment, Tiffany M. Phillips, William H. McBride, Ph.D., D.Sc., and Frank Pajonk, M.D., Ph.D., of the David Geffen School of Medicine at the University of California, Los Angeles, exposed such cells and normal breast cancer cells to a single or multiple doses of radiation.
More cancer-initiating cells survived radiation treatment than did the other breast cancer cells. For example, 46% of cancer-initiating cells survived treatment with 2 Gray of radiation compared with 20% of normal breast cancer cells. When cells were given clinical doses of radiation (3 Gray) each day for 5 days, the proportion of cancer-initiating cells increased. This, the scientists found, may happen because radiation treatment seems to activate a specific signaling pathway that prompts the cancer-initiating cells to self-renew.
In an editorial, Maximilian Diehn, M.D., Ph.D., and Michael F. Clarke, M.D., of the Stanford University School of Medicine, note that, among other limitations, the new study was conducted with tissue culture cells, which may not mimic the actual conditions of a tumor in a person. Nevertheless, the findings are provocative, they write. "The findings … have important clinical implications. In light of [this and other studies], it is even clearer that identifying and characterizing [cancer stem cells] for every tumor possible is of paramount importance and will likely lead to new therapeutic avenues."
Contact:
• Article: Enrique Rivero, UCLA Health Sciences media relations, 310-794-2273, erivero@mednet.ucla.edu; or Kim Irwin, Jonsson Cancer Center media relations, 310-206-2805, kirwin@mednet.ucla.edu
• Editorial: Lou Bergeron, Stanford Office of Communications, 650-723-0272, louisb3@stanford.edu
Statin Use Associated with Decreased Risk of Advanced Prostate Cancer
Use of cholesterol-lowering medications called statins is not associated with a lower risk of prostate cancer overall, but it is associated with a decreased risk of advanced disease, a large prospective study finds.
Two recently reported studies found an association between statin use and a reduced risk of prostate cancer. However, other observational studies and clinical trials have not confirmed those findings.
To investigate a possible association between statin use and the risk of prostate cancer and advanced prostate cancer, Elizabeth A. Platz, Sc.D., of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Md., and colleagues analyzed data from the Health Professionals Follow-up Study, a cohort of 34,989 U.S. men ages 40 to 75. From 1990 to 2002, the men were asked every other year about several factors, including use of cholesterol-lowering drugs.
In 1990, 4.4% of the men reported taking statins. By 2000, that number increased to 23.8%. Current statin use was not associated with risk of prostate cancer overall or of localized disease. However, current use of statins was associated with a reduced risk of advanced prostate cancer. Compared with men who had never taken statins, men currently taking statins had half the risk of advanced disease and less than half the risk of metastatic or fatal disease. The authors calculated that the incidence of advanced prostate cancer among current statin users was 38 cases per 100,000 men per year, and 89 cases per 100,000 men per year among nonusers. The inverse association was even stronger for metastatic and fatal prostate cancers combined, and the reduced risk of advanced disease was even lower with longer use of statins.
A possible confounding factor of the study is that more statin users than nonusers reported undergoing prostate-specific antigen (PSA) screening, a test often used as an early indicator of prostate cancer. Men who underwent multiple PSA tests were more likely to be diagnosed with localized prostate cancer and less likely to be diagnosed with advanced disease. The authors calculated that PSA screening did not account for their results, but they caution that it may have been a source of bias in the analysis.
"… It is premature to recommend the use of statins for the prevention of advanced prostate cancer," the authors write. "Further work is needed to address the role of PSA screening as a possible explanation for these findings and to identify the biologic mechanisms that may underlie the inverse association, if this association is indeed causal."
Contact: Vanessa Wasta, Johns Hopkins Kimmel Cancer Center Office of Public Affairs, 410-614-2916, wastava@jhmi.edu
Asthma Medicine Halts Pancreatic Cancer Cell Growth
A common asthma drug reduced pancreatic cancer cell growth in laboratory experiments and animal tests, a new study reports.
A protein called S100P is found in excess amounts in some cancers and is important for pancreatic cancer cell growth and survival. This protein also activates a cell surface protein receptor called RAGE that plays a role in Alzheimer disease, diabetes, and cancer.
A drug called cromolyn, an allergy and asthma treatment, has been shown to bind to proteins similar to S100P. To test cromolyn’s effects on S100P in pancreatic cancer cells, Thiruvengadam Arumugam, Ph.D., Vijaya Ramachandran, Ph.D., and Craig D. Logsdon, Ph.D., of the University of Texas M. D. Anderson Cancer Center in Houston, conducted experiments with the drug in tissue cultures and in mice with implanted pancreatic cancer.
They found that cromolyn bound to S100P, halted the activation of RAGE, and slowed cancer cell growth and survival in cell lines. In mice, the drug slowed pancreatic tumor growth and improved the effectiveness of gemcitabine, a chemotherapy drug used to treat pancreatic cancer.
"Together, these data support the further investigation of cromolyn as a possible treatment for pancreatic cancer," the authors write.
Contact: Scott Merville, M. D. Anderson Cancer Center External Communications, 713-792-0661, sdmervil@mdanderson.org
Model Predicts Risk of Leukemia Induced by Radiation Therapy
A new analysis shows that it may be possible to accurately predict a cancer patient’s risk of developing leukemia as a result of receiving radiation therapy for a primary tumor. Understanding these risks may help doctors optimize radiation treatment to minimize the side effects of this therapy, the authors say.
Radiotherapy inevitably exposes healthy tissue to radiation and increases the risk of radiation-induced cancer, the authors write. However, it is difficult to predict these risks because cancer radiotherapy has changed markedly in recent years, patients are on average younger than they used to be, and many cancer patients are surviving longer.
In the December 20 issue of JNCI, Igor Shuryak, M.D., and David J. Brenner, Ph.D., D.Sc., of Columbia University Medical Center in New York, and colleagues report a biologically based model for radiation-induced leukemia risk following radiotherapy.
The new model, which extends their recent model for radiation-induced solid cancers, takes into account the migration of unique cell types involved in the development of leukemia. It calculates leukemia risk based on a patient’s radiation dose to each of the different bone marrow regions throughout the body. The authors conclude that these models may provide new insights into the mechanisms of radiation-induced cancers.
Contact: Elizabeth A. Streich, Columbia University Medical Center Office of Communications and External Relations, 212-305-6535, eas2125@columbia.edu
Also in the December 20 JNCI:
• Reduced Dietary Fat Intake May Decrease Breast Cancer Recurrence: http://www.eurekalert.org/emb_releases/2006-12/jotn-df121406.php
• Costs of Long-Course Palliative Radiotherapy Acceptable in Late-Stage Lung Cancer: http://www.eurekalert.org/emb_releases/2006-12/jotn-ol121406.php
EMBARGOED FOR RELEASE: 19 DECEMBER 2006 16:00 EST
Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.
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JNCI Journal of the National Cancer Institute