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Abrupt increase in the cancerous cells, conventional therapies, including radiation and chemotherapy, often exhibit limited efficacy due to the heterogeneous nature of tumours, which can result in collateral damage to normal cells, severe haematological toxicities, and the development of drug resistance, ultimately compromising treatment outcomes and patient compliance. On the other hand, naturally sourced heterocyclic compounds can trigger functional versatility and play critical roles in various biochemical processes within living cells, enhancing their potential as therapeutic leads. Their ability to modulate multiple oncogenic signalling pathways influences key processes such as apoptosis, cell proliferation, migration, angiogenesis, and metastasis, thereby positioning them as promising candidates for improving chemotherapy efficacy, especially in resistant cases. With the rising costs of conventional treatments and the increasing cancer burden, there is an urgent demand for low-cost and sustainable alternatives. In view of that, natural heterocyclic bioactive compounds pave substantial advantages, including a broad chemical range with minimal toxicity and enhanced safety, making them compelling substitutes for synthetic drugs. This review illuminates the molecular mechanisms underlying the anti-cancer properties of significant heterocyclic structures from natural sources, emphasizing their potential to advance therapeutic strategies and emerging future clinical applications over the period of fifteen years.
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