Multi-target Drug Discovery for Cancer Therapy: A Contemporary Review

Abstract

Cancer remains one of the leading causes of mortality worldwide, with conventional therapies often limited by systemic toxicity, therapeutic resistance, and tumor heterogeneity. Multi-target drug discovery has emerged as a contemporary strategy to overcome these challenges, particularly through multi-kinase inhibitors and bispecific antibodies that simultaneously modulate multiple oncogenic pathways. This review integrates evidence from preclinical investigations, pivotal clinical trials, regulatory approvals, and key patent literature underpinning the development of multi-target anticancer agents. Representative multi-kinase inhibitors-including sorafenib, sunitinib, lenvatinib, cabozantinib, and regorafenib-are critically analyzed with respect to their molecular targets, therapeutic advantages, clinical performance, and associated intellectual property. Patented innovations covering kinase inhibition platforms, antibody engineering, and biomarkerbased cancer detection are also discussed. MKIs act by concurrently inhibiting multiple signaling kinases, such as vascular endothelial growth factor receptors, platelet-derived growth factor receptors, fibroblast growth factor receptors, mesenchymal-epithelial transition factor, rearranged during transfection, and rapidly accelerated fibrosarcoma, thereby suppressing angiogenesis, limiting compensatory signaling, and addressing tumor heterogeneity. Clinical trials demonstrate significant survival benefits in hepatocellular carcinoma, renal cell carcinoma, and thyroid cancer. Parallel advances in patented bispecific antibodies and epigenetic diagnostic technologies further expand the therapeutic and diagnostic landscape. Multi-targeting strategies delay resistance, reshape the tumor microenvironment, and improve outcomes, particularly when combined with immunotherapies or chemotherapies. However, challenges persist, including off-target toxicity, pharmacokinetic variability, high development costs, and limited accessibility. Patent trends reveal a growing emphasis on biomarker-guided patient selection, novel antibody formats, and rational combination therapies. MKIs and bispecific antibodies represent transformative modalities in modern oncology, supported by robust clinical evidence and extensive patent activity.