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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Monday, July 22, 2024
The combination of betulinic acid—a pentacyclic triterpene found naturally in plants that is a staple of anti-inflammatory, antiviral, and antibacterial folk remedies—and EGFR tyrosine kinase inhibitors (TKIs) gefitinib and osimertinib is showing preclinical efficacy in treating wild-type EGFR non–small cell lung cancer (NSCLC). According to the research results of Qi Wang, MD, PhD, of the Second Hospital of Dalian Medical University, China, and colleagues, published in Respiratory Research, betulinic acid may sensitize these TKIs to EGFR wild-type NSCLC. The investigators believe their findings “will ensure its eventual translation into clinical application.”
Specifically, betulinic acid seemed to suppress the cells’ proliferation and survival alike, and it induced autophagy-related cell death (although more research is needed to determine just how autophagy contributes to the death of cancer cells, the researchers said). The compound’s inhibitory activity was attributable to its interaction with the ATP-binding pocket of EGFR, wrote Dr. Wang and co-investigators. “It dramatically enhanced the suppressive effects of EGFR-TKIs by blocking EGFR and modulating the EGFR-ATK-mTOR axis…. The combination strategy activated EGFR-induced autophagic cell death, and… the EGFR-AKT-mTOR signaling pathway was essential for completing autophagy and cell-cycle arrest,” they continued.
Previous studies of betulinic acid and its bioactive derivatives led to the National Cancer Institute adding it to its RAID (Rapid Access to Intervention in Development) program, the authors noted. Another of its known attractive features is it has no cytotoxic effect on normal cells. The Respiratory Research study, however, is reportedly the first to show that betulinic acid works in wild-type EGFR NSCLC via direct binding with EGFR and regulating cellular pathways.
Disclosure: The study authors reported no conflicts of interest.
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