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

Coralie Reger de Moura; Marco Prunotto; Anjum Sohail; Maxime Battistella; Fanelie Jouenne; Daniel Marbach; Celeste Lebbé; Rafael Fridman; Samia Mourah

doi:10.3389/fonc.2020.01748

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

Front Oncol. 2020 Sep 11:10:1748. doi: 10.3389/fonc.2020.01748. eCollection 2020.

Authors

Coralie Reger de Moura^{1

2}, Marco Prunotto³, Anjum Sohail⁴, Maxime Battistella^{2

5}, Fanelie Jouenne^{1

2}, Daniel Marbach⁶, Celeste Lebbé^{2

7}, Rafael Fridman⁴, Samia Mourah^{1

2}

Affiliations

¹ Laboratory of Pharmacogenomics, Hôpital Saint-Louis, AP-HP, Paris, France.
² INSERM, UMR_S976, Université de Paris, Paris, France.
³ School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland.
⁴ Department of Pathology, School of Medicine, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States.
⁵ Department of Pathology, Hôpital Saint-Louis, AP-HP, Paris, France.
⁶ Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
⁷ Department of Dermatology, Hôpital Saint-Louis, AP-HP, Paris, France.

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.

Keywords: DDR1; MAPK inhibitors; drug resistance; melanoma; therapeutic target.

Publication types

Review