Mar 12 • 📝 Member Journeys & Results
Abstract 1875: Enhanced lung cancer treatment using AOH1996, a potent PCNA inhibitor
This has particular meaning, especially to all inflicted with the S4 lung adenoma(NSCLC) with EGFR mutation, and are already taking a 3rd generation EGFR TKI like Osimertinib (Tagrisso, or similar).
If you have S4 NSCLC with the EGFR TKI gene, and need to block the Ras-Raf-MEK-ERK (MAPK) pathway, then this is especially important:
ChatGPT said:
Blocking the Ras-Raf-MEK-ERK (MAPK) pathway is a promising strategy in cancer treatment, as this pathway is often hyperactivated in cancers driven by mutations in KRAS, NRAS, or BRAF. Below are some supplements, natural compounds, and repurposed drugs that have been found to inhibit different parts of this pathway.
1. Supplements & Natural Compounds
These natural compounds can modulate the Ras-Raf-MEK-ERK pathway through various mechanisms:
a) Resveratrol (from grapes, red wine)
- Inhibits Ras activation and MEK1/2
- Reduces ERK phosphorylation
- Anti-cancer effect: Induces apoptosis in Ras-driven cancers.
b) Curcumin (from turmeric)
- Blocks Raf and ERK phosphorylation
- Downregulates MEK-ERK activation
- Anti-cancer effect: Suppresses growth of melanoma, colorectal, and pancreatic cancer.
c) EGCG (Epigallocatechin Gallate, from green tea)
- Inhibits ERK phosphorylation
- Suppresses Ras activation
- Anti-cancer effect: Reduces cell proliferation in breast, lung, and prostate cancer.
d) Berberine (from Berberis plant)
- Inhibits ERK signaling in colorectal and breast cancer cells
- Induces apoptosis in Ras-driven cancers
- Enhances chemotherapy response.
e) Quercetin (from onions, apples)
- Blocks Ras signaling and ERK phosphorylation
- Induces cell cycle arrest in multiple cancers.
f) Sulforaphane (from broccoli, cruciferous vegetables)
- Inhibits ERK1/2 phosphorylation
- Suppresses Ras-driven cancer growth.
2. Repurposed Drugs That Block Ras-Raf-MEK-ERK
Several non-cancer drugs have been found to inhibit this pathway:
a) Metformin (Anti-diabetic)
- Inhibits MEK/ERK signaling
- Reduces tumor growth in KRAS-mutant cancers
- Activates AMPK, leading to inhibition of Raf-ERK signaling.
b) Simvastatin (Cholesterol-lowering statin)
- Inhibits Ras prenylation, preventing activation
- Blocks downstream Raf-MEK-ERK signaling.
c) Propranolol (Beta-blocker)
- Inhibits ERK activation
- Blocks proliferation of neuroblastoma and pancreatic cancer cells.
d) Hydroxychloroquine (Anti-malarial, autophagy inhibitor)
- Inhibits ERK phosphorylation in KRAS-mutant cancers.
- Enhances response to MEK inhibitors.
e) Celecoxib (NSAID, COX-2 inhibitor)
- Suppresses Ras-Raf-MEK-ERK pathway.
- Enhances apoptosis in KRAS-mutant colorectal cancer.
f) Disulfiram (Anti-alcoholism drug)
- Inhibits ERK phosphorylation
- Disrupts cancer stem cell signaling in Ras-mutant cancers.
3. Synergistic Combinations
- Metformin + Statins: Dual inhibition of Ras and downstream MEK/ERK.
- Curcumin + Quercetin: Synergistic inhibition of ERK signaling.
- EGCG + Sulforaphane: Enhances suppression of Ras-driven tumors.
- Hydroxychloroquine + MEK inhibitors: Improves MEK inhibitor response.
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Abstract 1875: Enhanced lung cancer treatment using AOH1996, a potent PCNA inhibitor
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