Even though there have been significant advances in drug discovery and molecular research to identify drug targets, the incidence and mortality rates associated with melanoma have been continuously rising.
Commonly used preventive strategies include mole screening followed by surgical removal of the benign nevi and abnormal moles. Nonetheless, the lack of effective screening programs and disease recurrence control after surgical procedures, increase the need for improved chemopreventive agents.
In a recent review, published in Advances in Pharmacology, Dr. SubbaRao V. Madhunapantula and Dr. Gavin P. Robertson, the Pennsylvania State University College of Medicine, reviewed the current knowledge concerning melanoma chemoprevention and the several different approaches used to achieve this goal.
Chemoprevention originally meant the use of agents that had the capacity to reverse, suppress, or prevent molecular or histologic premalignant lesions from developing into invasive cancer. Furthermore, chemoprevention was meant to treat patients who had received successful primary cancer treatment but were still at high risk of developing a second primary cancer.
Recently, the ability to delay cancer has also been considered a fundamental objective of chemoprevention.
Agents that can delay the onset of melanoma are considered of extreme importance, since minimal changes in early melanocytic lesion size can significantly change the 5-year survival rate.
Melanoma chemoprevention is still an underdeveloped research area and poses a challenge to the scientific and medical community. However, there have been recent studies trying to identify the molecular pathways responsible for initiating the malignant transformation of melanocytes to melanomas upon exposure to UV light, along with genetic and non-genetic factors that could be used as possible targets for chemoprevention, such as RAS-signaling in UV-induced melanomas.
There are 3 classes of melanoma chemopreventive agents: the ones that prevent melanoma occurrence in healthy individuals, the ones that prevent pre-malignant melanomas from developing into malignant melanomas and the ones that prevent melanomas to reoccur after getting treated for melanoma.
According to the authors, these agents should aim to inhibit “oncogenic kinases inducing the transformation of melanocytes and should trigger apoptosis in damaged melanocytes, while inducing DNA repair pathways to diminish UV-induced damage and prevent transformation”.
Preclinical and Phase I and II clinical studies have suggested that statins, antiproliferative, proapoptotic, angiostatic, anti-invasive and immunomodulatory compounds known to inhibit Ras proteins, could be used as chemopreventive agents against melanoma development. Furthermore, in vitro and in vivo studies have also suggested curcumin may play a chemopreventive role in melanoma.
Other possible chemopreventive agents include resveratrol, silymarin, epigallocatechin-3-gallate (EGCG), selenium-containing agents, non-steroidal anti-inflammatory drugs (NSAIDs), beta carotene, celecoxib,alpha-difluoromethylornithine (DFMO),betulinic acid, vitamin-D and sunscreens.
