Advanced Cancer Drug Development through Reverse Pharmacology: Integrating Traditional Knowledge and Herbal Therapies

Abstract: The global rise in cancer incidence, together with limitations of conventional therapies, including drug resistance, adverse effects, and high costs, underscores the need for innovative and multi-target treatment strategies. Reverse Pharmacology (RP) offers a translational framework that integrates traditional medical knowledge, particularly from Ayurveda, into modern oncology. Unlike conventional drug discovery, RP begins with clinically documented traditional remedies and progresses through experimental validation, mechanistic elucidation, and formulation standardization. This strategy may be advantageous for complex diseases like cancer, which often require multimodal therapeutic interventions. Medicinal plants such as Curcuma longa, Withania somnifera, and Tinospora cordifolia show notable anticancer potential by modulating key molecular targets, including NF-κB, PI3K/Akt, STAT3, and p53. Their key phytoconstituents, such as curcumin, withaferin A, and berberine, exhibit anti-proliferative, pro-apoptotic, antiangiogenic, and anti-metastatic properties in diverse cancer models. Additionally, these botanicals are generally considered safe, supported by centuries of traditional use and increasing preclinical validation. RP may facilitate the development of plant-based therapeutics and promote evidence-based, patient-centric approaches in cancer care. This review highlights how RP bridges ethnomedical knowledge and scientific research, thereby encouraging the integration of bioactive plant compounds into modern oncological practice to deliver cost-effective, accessible, and personalized treatment solutions.