Immune Resistance and EGFR Antagonists in Colorectal Cancer
- PMID: 31370270
- PMCID: PMC6721348
- DOI: 10.3390/cancers11081089
Immune Resistance and EGFR Antagonists in Colorectal Cancer
Abstract
: Targeting the epidermal growth factor receptor (EGFR) either alone or in combination with chemotherapy in patients with RAS wild type metastatic colorectal cancer (mCRC) has revolutionized the treatment of CRC, but with less results than initially envisaged. In recent years, the discovery of multiple pathways leading to the escape from anti-EGFR therapy has revealed an enormous complexity and heterogeneity of human CRC due to the intrinsic genomic instability and immune/cancer cell interaction. Therefore, understanding the mechanistic basis of acquired resistance to targeted therapies represents a major challenge to improve the clinical outcomes of patients with CRC. The latest findings strongly suggest that complex molecular alterations coupled with changes of the immune tumor microenvironment may substantially contribute to the clinical efficacy of EGFR antagonist. In this review, we discuss the most recent findings that contribute to both primary and acquired anti-EGFR therapy resistance. In addition, we analyze how strategies aiming to enhance the favorable effects in the tumor microenvironment may contribute to overcome resistance to EGFR therapies.
Keywords: EGFR; colorectal cancer; immune microenvironment; resistance; targeted therapies.
Conflict of interest statement
The authors declare no conflict of interest.
Figures


Similar articles
-
Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies.J Exp Clin Cancer Res. 2021 Oct 18;40(1):328. doi: 10.1186/s13046-021-02130-2. J Exp Clin Cancer Res. 2021. PMID: 34663410 Free PMC article. Review.
-
Molecular dissection of effector mechanisms of RAS-mediated resistance to anti-EGFR antibody therapy.Oncotarget. 2017 Jul 11;8(28):45898-45917. doi: 10.18632/oncotarget.17438. Oncotarget. 2017. PMID: 28507280 Free PMC article.
-
Mechanisms of resistance to anti-EGFR therapy in colorectal cancer.Oncotarget. 2017 Jan 17;8(3):3980-4000. doi: 10.18632/oncotarget.14012. Oncotarget. 2017. PMID: 28002810 Free PMC article. Review.
-
Therapeutic Strategies in Diseases of the Digestive Tract - 2015 and Beyond Targeted Therapies in Colon Cancer Today and Tomorrow.Dig Dis. 2016;34(5):574-9. doi: 10.1159/000445267. Epub 2016 Jun 22. Dig Dis. 2016. PMID: 27332557
-
Therapeutic value of EGFR inhibition in CRC and NSCLC: 15 years of clinical evidence.ESMO Open. 2016 Sep 16;1(5):e000088. doi: 10.1136/esmoopen-2016-000088. eCollection 2016. ESMO Open. 2016. PMID: 27843640 Free PMC article. Review.
Cited by
-
Visual Analysis of Colorectal Cancer Immunotherapy: A Bibliometric Analysis From 2012 to 2021.Front Immunol. 2022 Mar 31;13:843106. doi: 10.3389/fimmu.2022.843106. eCollection 2022. Front Immunol. 2022. PMID: 35432385 Free PMC article.
-
Molecular testing for colorectal cancer: Clinical applications.World J Gastrointest Oncol. 2021 Oct 15;13(10):1288-1301. doi: 10.4251/wjgo.v13.i10.1288. World J Gastrointest Oncol. 2021. PMID: 34721767 Free PMC article. Review.
-
Colorectal Cancer Stem Cells in the Progression to Liver Metastasis.Front Oncol. 2020 Aug 20;10:1511. doi: 10.3389/fonc.2020.01511. eCollection 2020. Front Oncol. 2020. PMID: 32974184 Free PMC article. Review.
-
Identification and validation of immunotherapy for four novel clusters of colorectal cancer based on the tumor microenvironment.Front Immunol. 2022 Oct 28;13:984480. doi: 10.3389/fimmu.2022.984480. eCollection 2022. Front Immunol. 2022. PMID: 36389763 Free PMC article.
-
Caffeine and its main targets of colorectal cancer.World J Gastrointest Oncol. 2020 Feb 15;12(2):149-172. doi: 10.4251/wjgo.v12.i2.149. World J Gastrointest Oncol. 2020. PMID: 32104547 Free PMC article. Review.
References
-
- Sartore-Bianchi A., Siena S., Tonini G., Bardelli A., Santini D. Overcoming dynamic molecular heterogeneity in metastatic colorectal cancer: Multikinase inhibition with regorafenib and the case of rechallenge with anti-EGFR. Cancer Treat Rev. 2016;51:54–62. doi: 10.1016/j.ctrv.2016.10.006. - DOI - PubMed
Publication types
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous