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Review
. 2023 Feb 23;11(3):678.
doi: 10.3390/biomedicines11030678.

Overcoming EGFR Resistance in Metastatic Colorectal Cancer Using Vitamin C: A Review

Ahmad Machmouchi  1 , Laudy Chehade  1 , Sally Temraz  1 , Ali Shamseddine  1
Affiliations
Review

Overcoming EGFR Resistance in Metastatic Colorectal Cancer Using Vitamin C: A Review

Ahmad Machmouchi et al. Biomedicines. .

Abstract

Targeted monoclonal antibody therapy against Epidermal Growth Factor Receptor (EGFR) is a leading treatment modality against metastatic colorectal cancer (mCRC). However, with the emergence of KRAS and BRAF mutations, resistance was inevitable. Cells harboring these mutations overexpress Glucose Transporter 1 (GLUT1) and sodium-dependent vitamin C transporter 2 (SVCT2), which enables intracellular vitamin C transport, leading to reactive oxygen species generation and finally cell death. Therefore, high dose vitamin C is proposed to overcome this resistance. A comprehensive search strategy was adopted using Pubmed and MEDLINE databases (up to 11 August 2022). There are not enough randomized clinical trials to support its use in the clinical management of mCRC, except for a subgroup analysis from a phase III study. High dose vitamin C shows a promising role in overcoming EGFR resistance in mCRC with wild KRAS mutation with resistance to anti-epidermal growth factor inhibitors and in patients with KRAS and BRAF mutations.

Keywords: BRAF mutation; EGFR Resistance; KRAS mutation; ascorbic acid; colorectal cancer; vitamin C.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cross talk between MAPK, PI3K, and Wnt pathway in CRC.
Figure 2
Figure 2
Proposed mechanism for increased ROS production in L-Ascorbic Acid-treated cells overexpressing either GLUT-1 or SVCT-2.
See this image and copyright information in PMC

References

    1. Sawicki T., Ruszkowska M., Danielewicz A., Niedźwiedzka E., Arłukowicz T., Przybyłowicz K.E. A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers. 2021;13:2025. doi: 10.3390/cancers13092025. - DOI - PMC - PubMed
    1. Biller L.H., Schrag D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA. 2021;325:669–685. doi: 10.1001/jama.2021.0106. - DOI - PubMed
    1. Böttger F., Vallés-Martí A., Cahn L., Jimenez C.R. High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer. J. Exp. Clin. Cancer Res. CR. 2021;40:343. doi: 10.1186/s13046-021-02134-y. - DOI - PMC - PubMed
    1. Yuan M., Wang Z., Lv W., Pan H. The Role of Anti-EGFR Monoclonal Antibody in mCRC Maintenance Therapy. Front. Mol. Biosci. 2022;9:870395. doi: 10.3389/fmolb.2022.870395. - DOI - PMC - PubMed
    1. Padayatty S.J., Levine M. Vitamin C: The known and the unknown and Goldilocks. Oral Dis. 2016;22:463–493. doi: 10.1111/odi.12446. - DOI - PMC - PubMed