title: p38α MAPK pathway: a key factor in colorectal cancer therapy and chemoresistance.
abstract: Colorectal cancer (CRC) remains one of the most common malignancies in the world. Although surgical resection combined with adjuvant therapy is effective at the early stages of the disease, resistance to conventional therapies is frequently observed in advanced stages, where treatments become ineffective. Resistance to cisplatin, irinotecan and 5-fluorouracil chemotherapy has been shown to involve mitogen-activated protein kinase (MAPK) signaling and recent studies identified p38α MAPK as a mediator of resistance to various agents in CRC patients. Studies published in the last decade showed a dual role for the p38α pathway in mammals. Its role as a negative regulator of proliferation has been reported in both normal (including cardiomyocytes, hepatocytes, fibroblasts, hematopoietic and lung cells) and cancer cells (colon, prostate, breast, lung tumor cells). This function is mediated by the negative regulation of cell cycle progression and the transduction of some apoptotic stimuli. However, despite its anti-proliferative and tumor suppressor activity in some tissues, the p38α pathway may also acquire an oncogenic role involving cancer related-processes such as cell metabolism, invasion, inflammation and angiogenesis. In this review, we summarize current knowledge about the predominant role of the p38α MAPK pathway in CRC development and chemoresistance. In our view, this might help establish the therapeutic potential of the targeted manipulation of this pathway in clinical settings.
authors.affiliation: Valentina Grossi, Alessia Peserico, Tugsan Tezil, Cristiano Simone, Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari "Aldo Moro", 70124 Bari, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Grossi
authors.affiliation: Valentina Grossi, Alessia Peserico, Tugsan Tezil, Cristiano Simone, Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari "Aldo Moro", 70124 Bari, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Peserico
authors.affiliation: Valentina Grossi, Alessia Peserico, Tugsan Tezil, Cristiano Simone, Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari "Aldo Moro", 70124 Bari, Italy.
authors.forename: Tugsan
authors.initials: T
authors.lastname: Tezil
authors.affiliation: Valentina Grossi, Alessia Peserico, Tugsan Tezil, Cristiano Simone, Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari "Aldo Moro", 70124 Bari, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Simone
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001343:Autophagy / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D048308:Mitogen-Activated Protein Kinase 14
keywords: Cell death; Chemoresistance; Colorectal cancer; Molecularly-targeted drugs; p38 mitogen-activated protein kinase
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