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      Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer

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          Abstract

          Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

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          Most cited references41

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          The blockade of immune checkpoints in cancer immunotherapy.

          Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
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            PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.

            Somatic mutations have the potential to encode "non-self" immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade.
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              Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer

              First-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial.
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                Author and article information

                Contributors
                Journal
                Therap Adv Gastroenterol
                Therap Adv Gastroenterol
                TAG
                sptag
                Therapeutic Advances in Gastroenterology
                SAGE Publications (Sage UK: London, England )
                1756-283X
                1756-2848
                28 June 2021
                2021
                : 14
                : 17562848211024460
                Affiliations
                [1-17562848211024460]Department of Hematology and Oncology, University of Tennessee Health Science Center, Memphis, TN, USA
                [2-17562848211024460]West Cancer Center and Research Institute, Germantown, TN, USA
                [3-17562848211024460]West Cancer Center and Research Institute, 7945 Wolf River Blvd, Germantown, TN 38138, USA
                Author notes
                Author information
                https://orcid.org/0000-0002-9341-6499
                Article
                10.1177_17562848211024460
                10.1177/17562848211024460
                8246487
                34262612
                14d9f77a-c43b-4bd6-8e67-5bb05eccf4a3
                © The Author(s), 2021

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 30 December 2020
                : 24 May 2021
                Categories
                Advances and Future Perspectives in Colorectal Cancer
                Review
                Custom metadata
                January-December 2021
                ts1

                colorectal cancer,mismatch repair deficiency,microsatellite instability,immunotherapy,pembrolizumab

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