title: Emerging Insight into MAPK Inhibitors and Immunotherapy in Colorectal Cancer.
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.
authors.affiliation: Department of Sciences and Technologies, University of Sannio, Via Port&apos;Arsa, 1182100 Benevento. Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pancione
authors.affiliation: CRO Aviano National Cancer Center, Aviano. Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Giordano
authors.affiliation: Department of Diagnostics and Public Health - Section of Pathology, University and Hospital Trust of Verona, 31134 Verona. Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Parcesepe
authors.affiliation: Department of Science and Technology, University of Sannio, Benevento. Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Cerulo
authors.affiliation: Medical Oncology and Anatomic Pathology Unit, San Filippo Neri Hospital, Rome. Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Coppola
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome. Italy.
authors.forename: Anais Del
authors.initials: AD
authors.lastname: Curatolo
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome. Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Conciatori
authors.affiliation: Division of Medical Oncology A, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome. Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Milella
authors.affiliation: Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, Complutense University, Madrid. Spain.
authors.forename: Almudena
authors.initials: A
authors.lastname: Porras
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D020928:Mitogen-Activated Protein Kinases
keywords: ERKs; MAPKs; colorectal cancer; immune check point inhibitors; immune resistance; immunotherapy; p38 MAPKs