V Debien, A Geraud-Cremieux, M Le Grand, D Carbone, I Garajova, C Pecoraro, E Pasquier, G J Peters, E Giovannetti, M Centanni, J Ciccolini
Personalized medicine has redefined oncology by tailoring treatments to molecular and clinical characteristics. However, despite remarkable advances in biomarker discovery and targeted therapy, the integration of pharmacological principles into precision oncology remains limited. The resulting discrepancy between biological innovation and therapeutic optimization contributes to high attrition rates in drug development, inconsistent real-world efficacy, and escalating financial toxicity. The European Organisation for Research and Treatment of Cancer Pharmacology and Molecular Mechanisms Group explored how pharmacology can bridge the gap between molecular precision and clinical reality. Although understanding mechanisms of action is a critical first step, the subsequent translation of this knowledge into individualized dosing and scheduling strategies and rational drug combinations is equally essential. Achieving this requires the use of quantitative tools, such as pharmacokinetic/pharmacodynamic modeling, therapeutic drug monitoring, and real-world evidence (RWE). These patient-centered approaches enable continuous learning from patient data, refine our understanding of exposure-response relationships, and support adaptive treatment strategies across diverse populations. We also discuss the rise of tumor-agnostic approvals, which transcend histological boundaries yet expose disparities in national regulatory and reimbursement frameworks. Ensuring equitable access to mechanism-driven therapies requires harmonized policies integrating pharmacological, clinical, and ethical perspectives. True personalization in oncology requires moving beyond target selection to delivering the right dose to the right patient at the right time. Embedding holistic pharmacology approaches into the design, evaluation, and postmarketing use of anticancer therapies will improve efficacy, minimize toxicity, and promote value-based care. Integrating mechanistic understanding with quantitative pharmacology and RWE represents the next frontier of precision oncology, transforming innovation into sustainable, patient-centered benefit.