Discoidin Domain Receptors in Melanoma: Potential Therapeutic Targets to Overcome MAPK Inhibitor Resistance.

Reger de Moura C; Prunotto M; Sohail A; Battistella M; Jouenne F; Marbach D; Lebbé C; Fridman R; Mourah S

doi:10.3389/fonc.2020.01748

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Journal article

Discoidin Domain Receptors in Melanoma: Potential Therapeutic Targets to Overcome MAPK Inhibitor Resistance.

Reger de Moura C Laboratory of Pharmacogenomics, Hôpital Saint-Louis, AP-HP, Paris, France.
Prunotto M School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.
Sohail A Department of Pathology, School of Medicine, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States.
Battistella M INSERM, UMR_S976, Université de Paris, Paris, France.
Jouenne F Laboratory of Pharmacogenomics, Hôpital Saint-Louis, AP-HP, Paris, France.
Marbach D Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Lebbé C INSERM, UMR_S976, Université de Paris, Paris, France.
Fridman R Department of Pathology, School of Medicine, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States.
Mourah S Laboratory of Pharmacogenomics, Hôpital Saint-Louis, AP-HP, Paris, France.

2020-10-05

Published in:

Frontiers in oncology. - 2020

English 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.

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