Abstract: Breast cancer remains a major public health challenge in India, with rising incidence and the limited efficacy of conventional chemotherapeutics driven by multidrug resistance (MDR), systemic toxicity, and therapeutic relapse. This review synthesizes emerging mechanistic evidence on repurposed synthetic agents and bioactive natural compounds, presenting a unified framework for mechanism-guided anti-cancer intervention. The selective estrogen receptor modulator (SERM) ormeloxifene exemplifies the promise of drug repurposing, exerting multi-target cytotoxicity through mitochondrial membrane depolarization, G0/G1 cell-cycle arrest, caspase-dependent apoptosis, ERα modulation, and disruption of proliferative signaling circuits. In parallel, potent natural products—including ellagitannins (corilagin, castalin, punicalagin) and triterpenoid saponins (α-hederin, D-rhamnose-β-hederin, quillaic acid, hederagenin)—demonstrate complementary mechanisms by enhancing intracellular ROS accumulation, suppressing PI3K/Akt and mTOR signaling, inhibiting NF-κB activation, and triggering intrinsic and extrinsic apoptotic pathways. Integrating these mechanistic axes, this review highlights a key innovation: both synthetic and phytochemical scaffolds converge on actionable molecular nodes governing survival signaling, metabolic rewiring, and MDR modulation. This convergence underscores their translational potential for developing combination or sequential regimens that enhance selectivity, circumvent drug resistance, and minimize off-target toxicity. Collectively, these mechanistically validated agents represent promising leads for preclinical optimization and rational design of next-generation, pathway-directed breast cancer therapeutics.
Samajdar et al. (Fri,) studied this question.
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