Targeting epidermal growth factor receptor and its downstream signaling pathways by natural products: A mechanistic insight

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.

Synthesis, characterization and biological research of novel 2-(quinoline-4-carbonyl)hydrazide-acrylamide hybrids as potential anticancer agents on MCF-7 breast carcinoma cells by targeting EGFR-TK

“…36 Therefore, EGFR-TK inhibitors have emerged as a promising area for drug creation and research study. 37 To provide mechanistic understanding of the anticancer potential of the most active hybrids, 2-(quinoline-4-carbonyl)hydrazide-acrylamide hybrids; 6a and 6h revealing the highest cytotoxic activity against breast carcinoma cell line, they were examined for their EGFR-TK inhibition activities. Results obtained as an IC 50 (μM) are presented in Fig.…”

Natural Prenylflavones from the Stem Bark of Artocarpus altilis: Promising Anticancer Agents for Oral Squamous Cell Carcinoma Targeting the Akt/mTOR/STAT-3 Signaling Pathway

“…Phytochemicals are known for their diverse chemical compositions, intricate structures, and pleiotropy, which have rendered them promising candidates for pharmacotherapy since ancient times. − Many of the isolated phytochemical entities sourced from diverse ethnomedicinal plants possess potential anticancer activities with enhanced selectivity toward cancer cells. − Consequently, it led to the development of novel chemotherapeutic drugs with broad implications for mankind. − The widespread accessibility of various plant species, straightforward extraction, isolation and purification methods, nontoxic nature, and the inherent manifestation of multiple pharmacological activities in these species collectively contribute to the establishment of environmentally sustainable and economical drug discovery processes . Our previous report had highlighted the efficacy of the bioactive triterpenoids, namely, betulinic acid and koetjapic acid, extracted from Dillenia indica in suppressing the survival and proliferation of oral cancer cells, bridging traditional insight with scientific authentication …”

“…Phytochemicals are known for their diverse chemical compositions, intricate structures, and pleiotropy, which have rendered them promising candidates for pharmacotherapy since ancient times. 17 − 19 Many of the isolated phytochemical entities sourced from diverse ethnomedicinal plants possess potential anticancer activities with enhanced selectivity toward cancer cells. 20 − 23 Consequently, it led to the development of novel chemotherapeutic drugs with broad implications for mankind.…”