The p38 MAPK Signaling Activation in Colorectal Cancer upon Therapeutic Treatments.

Angelina Pranteda,Deborah Fratantonio,Lorenzo Stramucci,Valentina Piastra,Gianluca Bossi

doi:10.3390/ijms21082773

Angelina Pranteda, Deborah Fratantonio + Show 3 more

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https://doi.org/10.3390/ijms21082773

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Pharmacological treatment of colorectal carcinoma currently proceeds through the administration of a combination of different chemotherapeutic agents. In the case of rectal carcinoma, radiation therapy also represents a therapeutic strategy. In an attempt at translating much-needed new targeted therapy to the clinics, p38 mitogen activated protein kinase (MAPK) inhibitors have been tested in clinical trials involving colorectal carcinoma patients, especially in combination with chemotherapy; however, despite the high expectations raised by a clear involvement of the p38 MAPK pathway in the response to therapeutic treatments, poor results have been obtained so far. In this work, we review recent insights into the exact role of the p38 MAPK pathway in response to currently available therapies for colorectal carcinoma, depicting an intricate scenario in which the p38 MAPK node presents many opportunities, as well as many challenges, for its perspective exploitation for clinical purposes.

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Colorectal cancer (CRC) is the third most common cancer, the fourth most common cause of cancer death, and the second most common cancer in terms of the number of individuals living with cancer five years after diagnosis worldwide [1]
In an attempt at translating much-needed new targeted therapy to the clinics, p38 mitogen activated protein kinase (MAPK) inhibitors have been tested in clinical trials involving colorectal carcinoma patients, especially in combination with chemotherapy; despite the high expectations raised by a clear involvement of the p38 MAPK pathway in the response to therapeutic treatments, poor results have been obtained so far
We review recent insights into the exact role of the p38 MAPK pathway in response to currently available therapies for colorectal carcinoma, depicting an intricate scenario in which the p38 MAPK node presents many opportunities, as well as many challenges, for its perspective exploitation for clinical purposes

Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer, the fourth most common cause of cancer death, and the second most common cancer in terms of the number of individuals living with cancer five years after diagnosis worldwide [1]. We recently reported [18], at least in CRC, that 5-FU exposure induces p38δ MAPK isoform activation sustaining pro-survival signals; in parallel, others and us observed that the p38α MAPK isoform is activated by 5-FU, and that this mediates the anti-tumor effect [12,19]. It was reported that p38 MAPK is able to support resistance to oxaliplatin and that, oxaliplatin-resistant CRC cells both display hyperactivation of p38 MAPK in response to oxaliplatin exposure and re-sensitization to the drug upon p38 MAPK pharmacological inhibition [36] These findings confirm that p38 MAPK modulation, even in the case of oxaliplatin, may mediate opposite effects, depending on the cell-specific context (Figure 1B)

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