Abstract: Cancer continues to be a major global health challenge, driving the need for innovative and precise therapeutic approaches. Protein kinases, which orchestrate vital cellular functions including cell division, survival, and metastasis, are frequently altered in malignancies, positioning them as highly promising targets for cancer treatment. Kinase inhibitors (KIs) have emerged as a powerful class of targeted therapies, demonstrating enhanced effectiveness and reduced systemic toxicity compared to traditional chemotherapy. This review explores the involvement of kinases in cancer development, with a focus on critical signalling cascades, such as MAPK, PI3K-AKT, and JAK-STAT. Kinase inhibitors are categorized based on their action mechanisms—ATPcompetitive, allosteric, reversible, and irreversible. Additionally, the review delves into medicinal chemistry approaches, including rational drug design, identification of pharmacophores, and insights from structure-activity relationship (SAR) analyses. Clinical use and pharmacological profiles of approved kinase inhibitors are highlighted, alongside ongoing challenges like therapeutic resistance and drug-induced toxicities, particularly affecting the heart and liver. To address these issues, recent efforts emphasize the design of advanced inhibitors, combination regimens, and novel drug delivery platforms. Cutting-edge strategies, such as PROTAC technology, dual-target agents, and artificial intelligence-guided drug discovery, are gaining momentum. Furthermore, the integration of personalized medicine is reshaping the selection and optimization of kinase-based therapies. In summary, although kinase inhibitors have significantly advanced cancer treatment, overcoming resistance, toxicity, and interpatient variability remains critical. Future progress hinges on the continued evolution of precision oncology and next-generation therapeutic innovations to maximize their clinical potential.
Sharma et al. (Wed,) studied this question.