CORONADO, CALIF. Some day patients may reach for Lipitor or Celebrex as a melanoma prevention agent, Dr. Michael E. Ming speculated at the annual meeting of the Pacific Dermatologic Association.
He described the ideal chemopreventive agent for melanoma as one that is effective, has an acceptable toxicity profile, and is already widely available.
One class of agents that could potentially meet those criteria if effectiveness in humans can be demonstrated is statins, which may prevent melanoma by decreasing production of intermediate products such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate in the pathway from 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) to cholesterol.
"These intermediate products may activate proteins important in cell growth and cell cycle progression, so decreased production of these products may lead to decreased activity of mutant forms of those proteins," said Dr. Ming, director of the pigmented lesion clinic at the University of Pennsylvania, Philadelphia.
Supportive evidence comes from several laboratory studies on melanoma cell lines and in mice, and from one clinical trial with melanoma as a secondary outcome (JAMA 1998;279:1615-22), and from a Dutch case-control study of statins and cancer in general (J. Clin. Oncol. 2004;22:2388-94). Other studies, however, have not shown a link between melanoma and statins, including meta-analyses and systematic reviews (JAMA 2006;295:74-80 and Cochrane Database Syst. Rev. 2005:CD003697), and it is difficult to say at this time whether statins are effective preventive agents against melanoma.
Nonsteroidal anti-inflammatory drugs (NSAIDs) represent another class of agents that may protect against melanoma, most likely through inhibition of cyclooxygenase-2 (COX-2), which in turn reduces prostaglandin production, Dr. Ming said.
Supportive evidence comes from a few laboratory studies on melanoma cell lines, including one case-control study in women (Oncol. Rep. 2001;8:655-7) and one case-control study in patients who already had melanoma (Dermatol. Surg. 2005;31:748-52). So far, though, the body of literature on this topic is too small and inadequate to state definitively that there is a link between NSAID use and lower rates of melanoma. In addition, some studies fail to show that COX-2 is expressed in all melanomas (Melanoma Res. 2001;11:587-99).
Other available agents that might help prevent melanoma include vitamins A, C, D, and E, but the current evidence in the medical literature is unclear, and it is difficult to draw meaningful conclusions, said Dr. Ming, who had no relevant conflicts of interest to disclose.
He emphasized that no candidate agent has been definitively established as having chemopreventive properties against melanoma. "Are there agents we can use against melanoma?" he asked. "The answer you have to say right now is not yet, but maybe soon."
'These intermediate products may activate proteins important in cell growth and cell cycle progression.' DR. MING