A Comprehensive Review of Triple-Negative Breast Cancer and Recent Advances in Acridone Derivatives for Its Treatment

Abstract

Triple-Negative Breast Cancer (TNBC) is an aggressive breast cancer, poorly responsive to drugs targeting hormone receptors in other breast cancer types. It is molecularly complex and aggressive, hindering therapy. Molecular characterization of TNBC has identified mutations and key signaling pathways in its development. Among these, epidermal growth factor receptor (EGFR) regulates cell proliferation, survival, migration, and metastasis. A literature review analyzed TNBC epidemiological, histopathological, and molecular features, especially EGFR-mediated signaling pathways and implications. ATP-competitive inhibition as an EGFR-targeted strategy was assessed. The pharmacology and structure–activity relationship (SAR) of acridone derivatives were explored for anticancer activity against TNBC. Evidence suggests EGFR overexpression contributes to TNBC progression and may be a target. ATP-competitive EGFR inhibitors could block EGFR and downstream pathways driving growth, survival, migration, and metastasis. Acridone derivatives show promise, and SARguided modifications may improve potency, selectivity, and pharmacokinetics for EGFR-based TNBC agents. EGFR-targeted acridone derivatives matter because few receptor-directed agents treat TNBC. Hurdles remain, including heterogeneity, acquired resistance, limited translation, and pharmacokinetic and safety issues. These may be addressed through structural optimization, biomarker-based selection, validation, and combinations for translation and precision medicine in TNBC patients. Acridone derivatives constitute a very promising scaffold for the design of therapeutics targeting EGFR in the treatment of TNBC. It is necessary that further structural modifications, along with biomarker-driven screening and preclinical investigation, be performed on these compounds.