Molecular Mechanisms of New and Re-purposed Synthetic as well as Natural Bioactive Molecules Against Breast Cancer:...

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• Breast cancer presents a significant health challenge in India, with increasing incidence and treatment failures due to multidrug resistance (MDR), toxicity, and relapse.
• Conventional chemotherapy efficacy is limited by systemic toxicity, therapeutic relapse, and the development of multidrug resistance (MDR).

Purpose of the Study:

• To review and synthesize mechanistic evidence on repurposed synthetic agents and natural compounds for mechanism-guided breast cancer intervention.
• To present a unified framework for developing novel, mechanism-directed breast cancer therapeutics by integrating insights from drug repurposing and natural products.

Main Methods:

• Literature review synthesizing mechanistic evidence on repurposed synthetic agents and bioactive natural compounds.
• Analysis of mechanisms of action, including cytotoxicity, cell-cycle arrest, apoptosis, receptor modulation, and signaling pathway inhibition.
• Integration of findings to identify converging molecular targets and translational potential.

Main Results:

• The selective estrogen receptor modulator (SERM) ormeloxifene exhibits multi-target cytotoxicity via mitochondrial depolarization, cell-cycle arrest, and apoptosis.
• Natural products like ellagitannins and triterpenoid saponins induce apoptosis and inhibit key survival pathways (PI3K/Akt, mTOR, NF-κB).
• Both synthetic and natural agents converge on molecular nodes regulating survival signaling, metabolic reprogramming, and MDR modulation.

Conclusions:

• Repurposed drugs and natural compounds offer promising leads for breast cancer treatment by targeting common molecular pathways.
• Integrating these agents in combination or sequential regimens can enhance selectivity, overcome MDR, and minimize toxicity.
• Mechanistically validated agents represent a foundation for preclinical optimization and rational design of next-generation breast cancer therapeutics.