期刊
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
卷 21, 期 14, 页码 1783-1792出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1871520621666201222143213
关键词
Epidermal growth factor receptor; breast cancer stem cells; breast cancer; tyrosine kinase inhibitors; monoclonal antibodies; antibody-drug conjugates
资金
- Council of Scientific and Industrial Research (CSIR) , Ministry of Science & Technology, Government of India [MLP0052, MLP0053]
- CSIR-JRF/SRF [IICT/Pubs./2020/193]
EGFR, a crucial transmembrane protein with tyrosine kinase activity, is overexpressed in various cancers triggering tumor progression and drug resistance; Inhibition of EGFR modulates chemosensitivity in breast cancer stem cells, serving as a potential drug target for breast cancer mitigation; Tyrosine kinase inhibitors and monoclonal antibodies targeting EGFR have been developed and approved for clinical use against breast cancer.
Epidermal Growth Factor Receptor (EGFR), a type-I transmembrane protein with intrinsic tyrosine kinase activity, is activated by peptide growth factors such as EGF, epigen, amphiregulin, etc. EGFR plays a vital role in regulating cell growth, migration, and differentiation in various tissue-specific cancers. It has been reported to be overexpressed in lung, head, and neck, colon, brain, pancreatic, and breast cancer that triggers tumor progression and drug resistance. EGFR overexpression alters the signaling pathway and induces cell division, invasion, and cell survival. Our prior studies demonstrated that EGFR inhibition modulates chemosensitivity in breast cancer stem cells, thereby serving as a potential drug target for breast cancer mitigation. Tyrosine kinase inhibitors (Lapatinib, Neratinib) and monoclonal antibodies (Trastuzumab) targeting EGFR have been developed and approved by the US FDA for clinical use against breast cancer. This review highlights the critical role of EGFR in breast cancer progression and enumerates the various approaches being undertaken to inhibit aggressive breast cancers by suppressing the downstream pathways. Furthermore, the mechanisms of action of potential molecules at various stages of drug development, as well as clinically approved drugs for breast cancer treatment, are illustrated.
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