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      Recent Advances in Monoclonal Antibody Therapy for Colorectal Cancers

      review-article
      Author(s): , , , *
      Publication date (Electronic):
      Journal: Biomedicines
      Publisher: MDPI
      Keywords: colorectal cancer, monoclonal antibody, therapeutic target, therapy

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          Abstract

          Colorectal cancer (CRC) is one of the leading causes of cancer deaths worldwide. Recent advances in recombinant DNA technology have led to the development of numerous therapeutic antibodies as major sources of blockbuster drugs for CRC therapy. Simultaneously, increasing numbers of therapeutic targets in CRC have been identified. In this review, we first highlight the physiological and pathophysiological roles and signaling mechanisms of currently known and emerging therapeutic targets, including growth factors and their receptors as well as immune checkpoint proteins, in CRC. Additionally, we discuss the current status of monoclonal antibodies in clinical development and approved by US Food and Drug Administration for CRC therapy.

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          Comprehensive Molecular Characterization of Human Colon and Rectal Cancer

          Nikolaus Schultz (2014)
          Summary To characterize somatic alterations in colorectal carcinoma (CRC), we conducted genome-scale analysis of 276 samples, analyzing exome sequence, DNA copy number, promoter methylation, mRNA and microRNA expression. A subset (97) underwent low-depth-of-coverage whole-genome sequencing. 16% of CRC have hypermutation, three quarters of which have the expected high microsatellite instability (MSI), usually with hypermethylation and MLH1 silencing, but one quarter has somatic mismatch repair gene mutations. Excluding hypermutated cancers, colon and rectum cancers have remarkably similar patterns of genomic alteration. Twenty-four genes are significantly mutated. In addition to the expected APC, TP53, SMAD4, PIK3CA and KRAS mutations, we found frequent mutations in ARID1A, SOX9, and FAM123B/WTX. Recurrent copy number alterations include potentially drug-targetable amplifications of ERBB2 and newly discovered amplification of IGF2. Recurrent chromosomal translocations include fusion of NAV2 and WNT pathway member TCF7L1. Integrative analyses suggest new markers for aggressive CRC and important role for MYC-directed transcriptional activation and repression.
          Article 0 comments Cited 1471 times – based on 0 reviews     Review now
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            Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study

            Rebecca Moss, Michael Axelson, Andrew Hill … (2017)
            Metastatic DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer has a poor prognosis after treatment with conventional chemotherapy and exhibits high levels of tumour neoantigens, tumour-infiltrating lymphocytes, and checkpoint regulators. All of these features are associated with the response to PD-1 blockade in other tumour types. Therefore, we aimed to study nivolumab, a PD-1 immune checkpoint inhibitor, in patients with dMMR/MSI-H metastatic colorectal cancer.
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              Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors.

              Fatima Haggar, Robin P Boushey (2009)
              In this article, the incidence, mortality, and survival rates for colorectal cancer are reviewed, with attention paid to regional variations and changes over time. A concise overview of known risk factors associated with colorectal cancer is provided, including familial and hereditary factors, as well as environmental lifestyle-related risk factors such as physical inactivity, obesity, smoking, and alcohol consumption.
              Article 0 comments Cited 689 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biomedicines
                Journal ID (iso-abbrev): Biomedicines
                Journal ID (publisher-id): biomedicines
                Title: Biomedicines
                Publisher: MDPI
                ISSN (Electronic): 2227-9059
                Publication date (Electronic): 05 January 2021
                Publication date Collection: January 2021
                Volume: 9
                Issue: 1
                Electronic Location Identifier: 39
                Affiliations
                Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul 02707, Korea; kyusang@ 123456kookmin.ac.kr (K.H.); yoonjinhwan8090@ 123456kookmin.ac.kr (J.H.Y.); 707jh@ 123456kookmin.ac.kr (J.H.L.)
                Author notes
                [* ]Correspondence: Lees2018@ 123456kookmin.ac.kr ; Tel.: +82-2-910-6763
                [†]

                These authors contributed equally to this work.

                Article
                Publisher ID: biomedicines-09-00039
                DOI: 10.3390/biomedicines9010039
                PMC ID: 7824816
                PubMed ID: 33466394
                SO-VID: 1a60edb1-6590-4dc9-bec0-d2b7395de1a4
                Copyright © © 2021 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 30 November 2020
                Date accepted : 31 December 2020
                Categories
                Subject: Review

                Keywords: colorectal cancer,monoclonal antibody,therapeutic target,therapy
                Data availability:
                Keywords: colorectal cancer, monoclonal antibody, therapeutic target, therapy

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