Targeting epidermal growth factor receptor and its downstream signaling pathways by natural products: A mechanistic
Rutuja Damare1, Kritika Engle1, Gautam Kumar1
1Department of Natural Products, Chemical Sciences, National Institute of Pharmaceutical Education and Research-Hyderabad, Hyderabad, India.
Abstract:
The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase (RTK) that maintains normal tissues and cell signaling pathways. EGFR is overactivated and overexpressed in many malignancies, including breast, lung, pancreatic, and kidney. Further, the EGFR gene mutations and protein overexpression activate downstream signaling pathways in cancerous cells, stimulating the growth, survival, resistance to apoptosis, and progression of tumors. Anti-EGFR therapy is the potential approach for treating malignancies and has demonstrated clinical success in treating specific cancers. The recent report suggests most of the clinically used EGFR tyrosine kinase inhibitors developed resistance to the cancer cells. This perspective provides a brief overview of EGFR and its implications in cancer. We have summarized natural products-derived anticancer compounds with the mechanistic basis of tumor inhibition via the EGFR pathway. We propose that developing natural lead molecules into new anticancer agents has a bright future after clinical investigation.
Insights
Epidermal growth factor receptor (EGFR) plays a role in cancer. Natural compounds targeting EGFR show promise for developing new anticancer agents, offering hope against drug resistance.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) crucial for normal tissue maintenance and cell signaling.
- EGFR is frequently overactivated and overexpressed in various cancers, including breast, lung, pancreatic, and kidney malignancies.
- EGFR mutations and overexpression drive tumor growth, survival, and resistance to apoptosis by activating downstream signaling pathways.
Purpose of the Study:
- To provide an overview of EGFR's role in cancer.
- To summarize natural products with anticancer properties that target the EGFR pathway.
- To explore the potential of natural compounds as novel anti-EGFR cancer therapeutics.
Main Methods:
- Literature review of EGFR's function in cancer.
- Summary of natural products and their mechanisms of action against EGFR.
- Analysis of EGFR-targeted natural compounds for therapeutic potential.
Main Results:
- EGFR signaling is a key driver in numerous cancers.
- Natural products exhibit anticancer effects through inhibition of EGFR signaling pathways.
- Existing anti-EGFR therapies face challenges with drug resistance.
Conclusions:
- Natural product-derived compounds offer a promising avenue for developing new anticancer agents targeting EGFR.
- Further clinical investigation of natural lead molecules is warranted for their development into effective cancer therapies.
- Developing natural compounds may overcome resistance issues associated with current EGFR inhibitors.
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