Exploring the therapeutic potential of withaferin A by modulating key oncosignaling pathways

Withaferin A (WA) is an effective withanolide compound derived from Withania somnifera that exhibits a multifaceted pharmacological profile, making it a promising candidate for managing several types of carcinomas. WA has been shown to regulate multiple oncosignaling pathways, proteins, and molecular determinants critical for cancer cell survival, proliferation, and resistance. Its pro-apoptotic, anti-metastasis, antiangiogenic, and anti-proliferative properties demonstrate its efficacy as a multitargeted anticancer agent to manage persistent challenges associated with the complex etiology of cancer. Although several investigations have shown the anticancer efficacy of WA, comprehensive insights into the multitargeted modulation of oncosignaling pathways and synergistic therapeutic potential remain fragmented. Therefore, this review focused on bridging these gaps by providing an integrated overview of WA's mechanistic and translational relevance in cancer therapy. Specifically, this review explores the therapeutic potential of WA in targeting key oncogenic pathways, which are implicated in various types of malignancies. Additionally, this study illustrates the synergistic role of WA in combination with current cancer therapies including immunotherapy, radiation, and chemoradiotherapy. Alongside investigating WA's pharmacological potential as an anticancer agent, this study also examines its pharmacokinetics, bioavailability, and toxicity profile.