Authors:	Haist, Maximilian Stege, Henner Kuske, Michael Bauer, Julia Klumpp, Annika Grabbe, Stephan Bros, Matthias
Title:	Combination of immune-checkpoint inhibitors and targeted therapies for melanoma therapy : the more, the better?
Online publication date:	21-Apr-2023
Year of first publication:	2023
Language:	english
Abstract:	The approval of immune-checkpoint inhibitors (CPI) and mitogen activated protein kinase inhibitors (MAPKi) in recent years significantly improved the treatment management and survival of patients with advanced malignant melanoma. CPI aim to counter-act receptor-mediated inhibitory effects of tumor cells and immunomodulatory cell types on effector T cells, whereas MAPKi are intended to inhibit tumor cell survival. In agreement with these complementary modes of action preclinical data indicated that the combined application of CPI and MAPKi or their optimal sequencing might provide additional clinical benefit. In this review the rationale and preclinical evidence that support the combined application of MAPKi and CPI either in concurrent or consecutive regimens are presented. Further, we will discuss the results from clinical trials investigating the sequential or combined application of MAPKi and CPI for advanced melanoma patients and their implications for clinical practice. Finally, we outline mechanisms of MAPKi and CPI cross-resistance which limit the efficacy of currently available treatments, as well as combination regimens.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-9017
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Cancer and metastasis reviews Version of Record (VoR)
Publisher:	Springer Science + Business Media B.V.
Publisher place:	Dordrecht u.a.
Issue date:	2023
ISSN:	1573-7233
Publisher DOI:	10.1007/s10555-023-10097-z
Appears in collections:	DFG-491381577-H