Genetics of melanoma chemoresistance

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."

add to favorites email to friend print save as pdf

Related Stories

Viral mimic induces melanoma cells to digest themselves

Aug 03, 2009

Recent research has uncovered an unexpected vulnerability in deadly melanoma cells that, when exploited, can cause the cancer cells to turn against themselves. The study, published by Cell Press in the August issue of the ...

Recommended for you

Gene test aids cancer profile

3 hours ago

The first round of chemotherapy did little to suppress Ron Bose's leukemia. The second round, with 10 times the dose, knocked the proliferating blast cells down, but only by half.

How a common antacid could lead to cheaper anti-cancer drugs

20 hours ago

A popular indigestion medication can increase survival in colorectal cancer, according to research published in ecancermedicalscience. But in fact, scientists have studied this for years - and a group of cancer advocates want t ...

User comments

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.