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      Immune Checkpoint Inhibitor-Based Combination Therapy for Colorectal Cancer: An Overview

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          Abstract

          Colorectal cancer (CRC) is one of the most common diseases in the world. Tumor immunotherapy is an innovative cancer treatment that acts by activating the human body’s autoimmune system. Immune checkpoint block has been shown to be effective in DNA deficient mismatch repair/microsatellite instability-high CRC. However, the therapeutic effect for proficient mismatch repair/microsatellite stability patients still requires further study and optimization. At present, the main CRC strategy is to combine other therapeutic methods, such as chemotherapy, targeted therapy, and radiotherapy. Here, we review the current status and the latest progress of immune checkpoint inhibitors in the treatment of CRC. At the same time, we consider therapeutic opportunities for transforming cold to hot, as well as perspectives on possible future therapies, which may be in great demand for drug-resistant patients.

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          Cancer statistics, 2022

          Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2022)
          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.
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            Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

            Dung Le, Jennifer N. Durham, Kellie N Smith … (2017)
            The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor-1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair-deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers' tissue of origin.
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              Pembrolizumab in Microsatellite-Instability–High Advanced Colorectal Cancer

              Thierry André, Kai-Keen Shiu, Tae Won Kim … (2020)
              Programmed death 1 (PD-1) blockade has clinical benefit in microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) tumors after previous therapy. The efficacy of PD-1 blockade as compared with chemotherapy as first-line therapy for MSI-H-dMMR advanced or metastatic colorectal cancer is unknown.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Gen Med
                Journal ID (iso-abbrev): Int J Gen Med
                Journal ID (publisher-id): ijgm
                Title: International Journal of General Medicine
                Publisher: Dove
                ISSN (Electronic): 1178-7074
                Publication date (Electronic): 26 April 2023
                Publication date Collection: 2023
                Volume: 16
                Pages: 1527-1540
                Affiliations
                [1 ]Department of Gastroenterology, Shidong Hospital of Shanghai , Shanghai, People’s Republic of China
                Author notes
                Correspondence: Xuanfu Xu, Department of Gastroenterology, Shidong Hospital of Shanghai , Shanghai, People’s Republic of China, Tel +86-021-25066666, Email shuanfusky@163.com
                Article
                Publisher ID: 408349
                DOI: 10.2147/IJGM.S408349
                PMC ID: 10149070
                PubMed ID: 37131870
                SO-VID: d3f5942f-c159-4cd8-b582-5ff9f856f41a
                Copyright © © 2023 Li and Xu.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 12 February 2023
                Date accepted : 19 April 2023
                Page count
                Figures: 1, References: 145, Pages: 14
                Categories
                Subject: Review

                ScienceOpen disciplines: Medicine
                Keywords: immune checkpoint inhibitors,colorectal cancer,pd-1/pd-l1,combination therapy,dna mismatch repair
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: immune checkpoint inhibitors, colorectal cancer, pd-1/pd-l1, combination therapy, dna mismatch repair

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