Overcoming EGFR Resistance in Metastatic Colorectal Cancer Using Vitamin C: A Review.
Ahmad MachmouchiLaudy ChehadeSally TemrazAli ShamseddinePublished in: Biomedicines (2023)
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.
Keyphrases
- epidermal growth factor receptor
- metastatic colorectal cancer
- high dose
- tyrosine kinase
- growth factor
- small cell lung cancer
- cell death
- reactive oxygen species
- phase iii
- wild type
- advanced non small cell lung cancer
- monoclonal antibody
- low dose
- open label
- blood pressure
- cell cycle arrest
- cell proliferation
- stem cells
- induced apoptosis
- double blind
- randomized controlled trial
- deep learning
- insulin resistance
- cell therapy
- big data
- machine learning
- signaling pathway
- smoking cessation