Authors : Tanjima Tarique Laskar, Hasina Mehnaj Laskar, Jiaul Ahmed Mazumder, Rupajit Bhattacharjee, Md Ikbal Husain, Bandana Das, Panchami Das, Paromita Dutta Choudhury, Monica Arora, Sudarshana Borah, Debarupa Chakraborty, Prithviraj Chakraborty, Amlan Das
DOI : 10.1007/s12672-025-03764-w
Volume : 16
Issue : 1
Year : 2025
Page No : 1-43
Breast cancer is a highly heterogeneous malignancy encompassing distinct molecularsubtypes such as Luminal A & B, HER2 enriched and triple negative breast cancer,each characterized by unique genomic, transcriptomic and proteomic landscapesthat dictate differential prognosis and therapeutic response. This review delineatesthe complex signalling pathways underlying breast cancer including estrogenreceptor, progesterone receptor and HER2 pathways and their downstream effectorssuch as PI3K/AKT/mTOR, RAS/MAPK, Notch, Wnt/β-catenin and JAK/STAT cascades.The interconnectivity of these pathways not only governs tumor cell proliferation,survival and metastasis but also contributes to intrinsic and acquired resistancemechanisms against standard-of-care therapies including endocrine agents, HER2-targeted antibodies and chemotherapy. Emerging therapeutic strategies such asnext-generation selective estrogen receptor degraders, proteolysis-targeting chimeras,antibody-drug conjugates, immune checkpoint inhibitors and pathway-specificsmall-molecule inhibitors highlights their mechanistic rationale, clinical evidence andbiomarker-guided applicability. Resistance mechanisms involving ESR1 mutations,PTEN loss, p95HER2 expression, BRCA reversions and tumor microenvironment-mediated immunosuppression contributes to therapy resistance. The review exploresmolecular subtypes, oncogenic signalling pathways, treatment approaches, resistancemechanisms including acquired resistance & crosstalk, metabolic reprogramming,epigenetic modifications, immune modulations and tumor microenvironment, spatialtranscriptomics insights into immune cell subsets & treatment response biomarkersand the role of artificial intelligence in breast cancer treatment. The integration ofartificial intelligence-based predictive modelling and rational drug combinationsoffers a promising paradigm for overcoming resistance and tailoring precisiononcology approaches. By comprehensively mapping these oncogenic factors andtherapeutic intersections, this review provides a strategic framework for optimizingbreast cancer management in the era of molecular medicine.