Genetics of melanoma chemoresistance

June 6, 2011

Malignant melanoma is a highly aggressive and notoriously chemoresistant form of cancer. In a new paper, Ohanna et al. reveal that anti-melanoma drugs may, paradoxically, induce a senescence-associated secretory profile ("secretome") that can ultimately promote metastasis and contribute to melanoma relapse.

While has been thought of as a natural mechanism to combat uncontrolled cell growth, or cancer, recent studies have shown that some cell types express a secretome during senescence that alters the tumor microenvironment and affects the cell's response to chemotherapeutic drugs. Ohanna et al. confirm that senescent do, in fact, express an inflammatory secretome, and have delineated the genetic pathways involved: Depletion of the MITF transcription factor, or exposure to anti-melanoma drugs, activates the and triggers senescence. Senescent melanoma cells express a PARP-1 and NF-kB—associated secretome, which contains high levels of the chemokine CCL2. CCL2, in turn, leads to a loss of E-cadherin expression and an invasive phenotype.

In fact, Ohanna et al. show that culturing melanoma cells with exogenous CCL2 enhances their survival and invasiveness. This finding suggests that blocking CCL2, or its upstream effectors, may represent a novel therapeutic pathway. As Dr. Bertolotto explains, "Our data disclose a part of the mechanisms contributory to failure of anti-melanoma chemotherapies and we gain valuable insight for the identification of new candidates, namely PARP-1, NF-kB or CCL2, for therapeutic intervention in view to overcome drug resistance."

Related Stories

Recommended for you

Combination therapy can prevent cytostatic resistance

November 26, 2015

Researchers at Karolinska Institutet have found a new way of preventing resistance to cytostatics used in the treatment of cancers such as medulloblastoma, the most common form of malignant brain tumour in children. The promising ...

Forecasting the path of breast cancer in a patient

November 23, 2015

USC researchers have developed a mathematical model to forecast metastatic breast cancer survival rates using techniques usually reserved for weather prediction, financial forecasting and surfing the Web.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.