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While multiple EGFR inhibitors have emerged, their therapeutic efficacy is constrained by the development of drug resistance and long\u2010term toxicity. Indoles have been identified as one of the promising scaffold classes to compete against EGFR in terms of selectivity and potency. They are favorable for anticancer drug discovery because they are structurally plastic, possess favorable pharmacokinetics, and bind to the ATP\u2010binding pocket of EGFR. Indole derivatives inhibit the auto\u2010phosphorylation of EGFR, thereby exhibiting their activity against cancers by blocking cancer cell proliferation, survival, and metastasis. The translation potential of this scaffold is also supported by the clinical success of indole\u2010based EGFR inhibitors, including the third\u2010generation drug osimertinib. Recent advances in molecular docking, structure\u2013activity relationship studies, and hybrid drug design highlight the potential of indole\u2010based scaffolds to address resistance mutations while minimizing side effects. This paper summarizes the relevant literature of indole EGFR inhibitors published between 2021 and 2025, which may include mechanistic insights, biological screening, and therapeutic potential. The indole scaffold can be a useful starting point to push forward the next generation of targeted cancer therapies.<\/jats:p>","DOI":"10.1002\/cbdv.202502968","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T10:30:47Z","timestamp":1770719447000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting EGFR With Indole Derivatives: Recent Advances and Therapeutic Perspectives"],"prefix":"10.1002","volume":"23","author":[{"given":"Tanishq","family":"Verma","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry School of Pharmaceutical Sciences Lovely Professional University  Phagwara India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7405-8809","authenticated-orcid":false,"given":"Anuradha","family":"Mehra","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry School 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