Emerging Insight into MAPK Inhibitors and Immunotherapy in Colorectal Cancer

Author(s): Massimo Pancione*, Guido Giordano, Pietro Parcesepe, Luigi Cerulo, Luigi Coppola, Anais Del Curatolo, Fabiana Conciatori, Michele Milella, Almudena Porras.

Journal Name: Current Medicinal Chemistry

Volume 24 , Issue 14 , 2017

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Abstract:

Our understanding of the genetic and non-genetic molecular alterations associated with colorectal cancer (CRC) progression and therapy resistance has markedly expanded in the recent years. In addition to their effects on tumor biology, targeted therapies can have effects on host immune responses. However, the mechanisms by which immune cells organize tumor microenvironments to regulate T-cell activity need to be comprehensively defined. There is good evidence in the literature that alterations in different members of the MAPK superfamily (mainly ERKs and p38 MAPKs) modify the inflammatory response and antitumor immunity, enhancing metastatic features of the tumors. In addition, a plethora of alterations that emerge at relapse often converge on the activation of MAPKs, particularly, ERKs, which act in concert with other oncogenic signals to modulate cellular homeostasis and clonal evolution during targeted therapies. Herein, we discuss how this knowledge can be translated into drug development strategies aimed at increasing tumor antigenicity and antitumor immune responses. Insights from these studies could provide a framework for considering additional combinations of targeted therapies and immunotherapies for the treatment of CRC.

Keywords: MAPKs, colorectal cancer, immune resistance, immune check point inhibitors, immunotherapy, ERKs, p38 MAPKs.

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Article Details

VOLUME: 24
ISSUE: 14
Year: 2017
Page: [1383 - 1402]
Pages: 20
DOI: 10.2174/0929867324666170227114356
Price: $58

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