Targeted cancer therapy kills prostate tumor cells, study finds

ScienceDaily (June 6, 2011) — A new targeted therapy for prostate cancer halts tumor growth in animals with advanced prostate cancer that is resistant to hormone therapy, a new study finds.

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The results are being presented at The Endocrine Society's 93rd Annual Meeting in Boston.

"This targeted therapy may provide a treatment breakthrough that will extend the lives of men with advanced, hormone-refractory prostate cancer," said lead investigator Shuk-mei Ho, PhD, chairwoman of the Department of Environmental Health at the University of Cincinnati.

Men with prostate cancer that has recurred or has spread outside the prostate routinely receive androgen deprivation therapy, which blocks the action of the male hormones. This castration occurs through surgical removal of both testes or more often with medications. Although effective, this hormone-blocking treatment eventually stops working in some patients, Ho said.

"These patients are left with very few treatment options and usually succumb quickly to the disease," she said.

Ho's team previously found they can inhibit the growth of prostate cancer cell lines in culture by targeting and activating a protein called G protein-coupled receptor 30 (GPR30) using the experimental drug G-1, a GPR30 agonist, or stimulator.

In their new study, funded by the Veterans Affairs and the National Institutes of Health, Ho and her co-workers tested G-1 in an animal model of castration-resistant prostate cancer. They implanted human prostate cancer cells beneath the skin of male mice. The established tumor regressed upon castration and after the cancer relapsed, they injected the mice with a low dose of G-1. They also gave G-1 to noncastrated, or "intact," male mice that had prostate tumors. In these intact mice that still had male hormones, G-1 did not stop growth of the prostate tumors or cause substantial death of tumor cells (necrosis), they found.

"Surprisingly, G-1 was highly effective in halting the growth of the tumors that re-emerged after castration," Ho said.

The castration-resistant tumors showed a 65 percent necrosis. These mice had increased expression of GPR30 after castration, which Ho believes sensitized prostate tumors to the cell growth-inhibiting effects of G-1.

"These results mean G-1 won't work without androgen deprivation therapy," she said.

Therefore, Ho reported, the window of time when this targeted therapy might be effective for treating hormone-resistant prostate cancer is after androgen deprivation therapy. She said she believes G-1 can make androgen blockade more effective. G-1 caused no harm to the prostate or other vital organs in mice, she added.

Although GPR30 may have a role in cell growth in female tissues, Ho said it appears to have the opposite effect in men with hormone-resistant prostate cancer. "The beauty of this GPR30 is that it does not have any estrogen, and so it will not cause any side effects of estrogen," she said.

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Benefit of targeted lung cancer therapy confirmed

ScienceDaily (June 3, 2011) — A drug that targets a specific type of lung cancer shows a dramatic response in more than half of the people who take it. The drug, called crizotinib, has been in clinical trials since 2006, and the results from the largest group of patients to take it within the first of these clinical trials are being presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

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The patients taking crizotinib have anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer (NSCLC) and the drug targets the gene that drives this particular kind of cancer. In 119 patients, crizotinib produces some degree of shrinkage in the tumors of the majority of patients with dramatic responses in more than 60 percent of cases. The responses last approximately 48 weeks.

D. Ross Camidge, MD, PhD, the director of the lung cancer clinical program at University of Colorado Hospital (UCH) and the University of Colorado Cancer Center, will be presenting the latest results from the crizotinib trial at ASCO. "The strength of crizotinib in ALK positive lung cancer was apparent when less than 20 patients were taking part in the trial. The benefit of targeting this kind of cancer with this particular drug has only been confirmed as more patients enrolled in the trial," said Camidge. "This demonstrates the efficacy of new drugs can be reliably revealed even among small groups of patients when the cancers being tested are molecularly uniform."

Medical oncologists at UCH care for one of the largest groups of ALK positive lung cancer patients in the world. Approximately one in 20 lung cancer patients is ALK positive -- their responses to crizotinib are dramatic, the side effects are usually mild and often improve over time.

Camidge believes the results being seen with crizotinib open the door to a new way of thinking when it comes to cancer treatment. "We need to continue testing drugs in molecularly defined populations to find out early whether they can be effective. When we try and give targeted drugs to everyone, knowing that cancers are so different between individuals, we run the risk of missing real breakthroughs that only apply to subgroups. You don't have to know definitively what the magic marker for who responds to a particular drug is when you start -- but you can test a series of hypotheses by prescreening patients and really focus on the development of drugs on the right group as early as possible."

Lung cancer is the leading cause of cancer deaths in the United States. Camidge said it is crucial for anyone diagnosed to get their lung tumor tested for ALK and an increasing list of other molecular markers. The University of Colorado helped to develop several of these tests that now reveal that lung cancer is actually several different diseases at the molecular level. Each one may need a different type of treatment.

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