Abstract
Melanoma is a highly malignant skin cancer with high propensity to metastasize and develop drug resistance, making it a difficult cancer to treat. Current therapies targeting BRAF (V600) mutations are initially effective, but eventually tumors overcome drug sensitivity and reoccur. This process is accomplished in part by reactivating alternate signaling networks that reinstate melanoma proliferative and survival capacity, mostly through reprogramming of receptor tyrosine kinase (RTK) signaling. Evidence indicates that the discoidin domain receptors (DDRs), a set of RTKs that signal in response to collagen, are part of the kinome network that confer drug resistance. We previously reported that DDR1 is expressed in melanomas, where it can promote tumor malignancy in mouse models of melanoma, and thus, DDR1 could be a promising target to overcome drug resistance. In this review, we summarize the current knowledge on DDRs in melanoma and their implication for therapy, with emphasis in resistance to MAPK inhibitors.
Highlights
Coralie Reger de Moura1,2, Marco Prunotto3, Anjum Sohail4, Maxime Battistella2,5, Fanelie Jouenne1,2, Daniel Marbach6, Celeste Lebbé2,7, Rafael Fridman4 and Samia Mourah1,2*
Evidence has shown that BRAF inhibitors (BRAFi) and MEKi therapeutic effects on BRAFV600-treated tumors are decreased by enhanced ERBB3 signaling, suggesting that ERBB3 is implicated in adaptive resistance to BRAF and MEK inhibitors
The emerging evidence suggests that discoidin domain receptors (DDRs) are part of the signaling networks that contribute to melanoma progression
Summary
Coralie Reger de Moura1,2, Marco Prunotto3, Anjum Sohail4, Maxime Battistella2,5, Fanelie Jouenne1,2, Daniel Marbach6, Celeste Lebbé2,7, Rafael Fridman4 and Samia Mourah1,2*. We previously reported that DDR1 is expressed in melanomas, where it can promote tumor malignancy in mouse models of melanoma, and DDR1 could be a promising target to overcome drug resistance. DDR2 together with DDR1 may contribute to the activation of signaling pathways associated with interactions of carcinoma cells with both network-forming and fibrillar collagens, as they traffic through various matrix compartments.
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