Efficacy and side effects of immune checkpoint inhibitors in the treatment of colorectal cancer.

Autor:	Manz SM; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Losa M; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Fritsch R; Center for Medical Oncology and Hematology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Scharl M; Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Raemistrasse 100, Zurich, CH-8091, Switzerland.
Jazyk:	angličtina
Zdroj:	Therapeutic advances in gastroenterology [Therap Adv Gastroenterol] 2021 Apr 15; Vol. 14, pp. 17562848211002018. Date of Electronic Publication: 2021 Apr 15 (Print Publication: 2021).
DOI:	10.1177/17562848211002018
Abstrakt:	Colorectal cancers (CRCs) remain one of the most common and challenging neoplasia in the Western world. The response rate of immunotherapeutic treatment approaches in a subset of advanced CRCs is remarkable and has sustainably changed treatment regimens. Unfortunately, currently available immunotherapeutics only displayed significant antitumoral activity - in terms of progression free survival (PFS) and objective response rate (ORR) - in microsatellite instability-high (MSI-H)/DNA mismatch repair deficient (dMMR) CRCs. Subsequently, these remarkable results had led to the US Food and Drug Administration's approval of both immune checkpoint inhibitors (ICIs) pembrolizumab and nivolumab in the treatment of advanced MSI-H/dMMR CRCs. However, in microsatellite stable (MSS)/DNA mismatch repair proficient (pMMR) CRCs, ICIs have clearly failed to meet their expectations and are therefore not considered effective. As the vast majority of CRCs display a molecular MSS/pMMR profile, current treatment approaches endeavor to improve tumor immunogenicity that consecutively leads to increased proinflammatory cytokine levels as well as tumor infiltrating T-cells, which in turn may be targeted by various immunotherapeutic agents. Therefore, ongoing studies are investigating novel synergistic therapy modalities and approaches to overcome a "cold" to "hot" tumor conversion in MSS/pMMR CRCs. In this review, we summarize the efficacy and possible immune-related adverse events as well as novel therapeutic approaches of ICIs in the treatment of MSI-H/dMMR and MSS/pMMR CRCs. Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest. (© The Author(s), 2021.)
Databáze:	MEDLINE
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