New findings from researchers in NCI's Center for Cancer Research (CCR) have shown that rapamycin, an immunosuppressant normally used to prevent the body from rejecting organ and bone marrow transplants and also used to coat cardiac stents, was highly effective in preventing the development of tobacco-related lung tumors in mice.
The study results, published in the April 1 Clinical Cancer Research, showed that rapamycin (also known as sirolimus) succeeded by inhibiting mTOR, a protein known to play a critical role in the development of certain lung tumors. This study tested rapamycin for treatment as well as prevention of lung cancer.
The researchers exposed the mice to NNK, a procarcinogen found in tobacco. Those given rapamycin beginning 1 week later, on alternate days, had a 90-percent drop in the number of tumors and a 74-percent drop in tumor size. Mice given rapamycin 26 weeks after exposure to NNK continued to develop tumors at the same rate as controls; however, the tumors were smaller and did not progress as quickly.
"Our studies provide an exciting link between exposure to an important tobacco carcinogen, NNK, and mTOR," said Dr. Phillip A. Dennis, head of the Signal Transduction Section in CCR's Medical Oncology Branch. "The critical question is whether this approach would be safe and effective in smokers at high risk for developing lung cancer. Given that rapamycin is relatively inexpensive and FDA-approved for other indications, we are designing clinical trials in humans to address these questions and hope to have the answers in the near future."
Further research is needed to determine whether doses of rapamycin that achieve an antitumor effect in mice are achievable in humans, and whether giving a dose that would be sufficient for an antitumor effect would cause unacceptable levels of immune suppression or toxicity.
New Prostate Cancer Guidelines Weigh Early Therapy, Watchful Waiting
Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of androgen deprivation therapy (ADT) to treat prostate cancer state that early ADT does not appear to offer a survival advantage over so-called watchful waiting for men with metastatic or progressive disease and, as a result, do not strongly recommend this treatment approach.
The guidelines were published in the April 2 issue of the Journal of Clinical Oncology and are available on the ASCO Web site. Among the materials reviewed by an expert advisory panel to develop the updated guidelines were results from recent randomized, controlled clinical trials, a meta-analysis, a systematic review, and data from several ongoing trials.
Based on its review, the panel concluded that, although early initiation of ADT did decrease the risk of prostate cancer-specific death by 17 percent, it increased the risk of overall mortality by 15 percent and, as a result, could not be endorsed as a favored option over watchful waiting.
"Doctors should discuss with patients the risks and benefits of early ADT versus deferred therapy," the guidelines' lead author, Dr. Andrew Loblaw from Toronto Sunnybrook Regional Cancer Centre, advised in a statement. "If the patient prefers to defer therapy, he should have regular visits with his doctor every 3 to 6 months to monitor the disease."
The guidelines also state that the available evidence suggests that when ADT therapy is initiated, bilateral orchiectomy or luteinizing hormone-releasing hormones (LHRH) are the recommended options. In addition, the panel found strong evidence to back the option of so-called combined androgen blockade, in which a nonsteroidal anti-androgen therapy is combined with an orchiectomy or LHRH.