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

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Targeted monoclonal antibody therapy against Epidermal Growth Factor Receptor (EGFR) is a primary treatment for metastatic colorectal cancer (mCRC).
• KRAS and BRAF mutations confer resistance to EGFR inhibitors.
• Mutated cells overexpress Glucose Transporter 1 (GLUT1) and sodium-dependent vitamin C transporter 2 (SVCT2), influencing intracellular vitamin C levels.

Purpose of the Study:

• To evaluate the potential of high-dose vitamin C to overcome resistance to EGFR inhibitors in mCRC.
• To explore the role of vitamin C in mCRC with specific genetic mutations.

Main Methods:

• A comprehensive literature search was conducted using PubMed and MEDLINE databases up to August 11, 2022.
• Analysis focused on studies investigating vitamin C as a therapeutic agent in mCRC, particularly in the context of EGFR resistance and genetic mutations.

Main Results:

• Limited randomized clinical trials exist, with evidence primarily from a subgroup analysis of a phase III study.
• High-dose vitamin C demonstrates potential in overcoming EGFR resistance in mCRC.
• This strategy appears effective in patients with wild-type KRAS resistant to anti-EGFR inhibitors and in those with KRAS and BRAF mutations.

Conclusions:

• High-dose vitamin C is a promising adjunctive therapy for overcoming resistance to EGFR inhibitors in mCRC.
• Further clinical trials are needed to establish definitive efficacy and optimal dosing.
• Vitamin C may offer a viable treatment option for specific patient subgroups with refractory mCRC.