Overcoming Drug Resistance and Optimizing Cancer Treatment Outcomes

Despite major advances in oncology, drug resistance remains one of the principal obstacles to achieving durable responses and cure in cancer patients. Both intrinsic and acquired resistance limit the effectiveness of cytotoxic agents, targeted therapies, endocrine therapies, immunotherapies, and antibody–drug conjugates, ultimately compromising survival and quality of life. A deeper pharmacological understanding of resistance mechanisms and their impact on drug exposure, target engagement, and downstream signaling is essential to design more effective and sustainable treatment strategies.This Research Topic, “Overcoming Drug Resistance and Optimizing Cancer Treatment Outcomes,” aims to bring together cutting-edge work that dissects the pharmacology of anti-cancer drugs in the context of resistance and treatment failure. We welcome studies spanning molecular, cellular, preclinical, translational, and early clinical research that clarify how resistance arises, how it can be predicted, and how it can be overcome or delayed through rational pharmacological interventions.We encourage submissions that address, but are not limited to, the following themes:Molecular and cellular mechanisms of resistance to chemotherapeutics, targeted therapies, endocrine therapies, and immunotherapies, including alterations in drug targets, bypass signaling, epigenetic changes, and tumor heterogeneity.Pharmacokinetic and pharmacodynamic determinants of resistance, such as altered absorption, distribution, metabolism, and excretion, changes in drug transporters and metabolizing enzymes, or impaired target engagement.Tumor microenvironment and resistance, including hypoxia, stromal interactions, immune evasion, and their pharmacological modulation.Combination strategies and sequencing approaches designed to prevent, delay, or overcome resistance, including rational drug combinations, vertical and horizontal pathway inhibition, and integration of immunotherapy with targeted or cytotoxic agents.Biomarkers and predictive tools for resistance and treatment response, including pharmacogenomics, liquid biopsies, and pharmacometric or modeling approaches that inform dose optimization and treatment adaptation.Novel anti-cancer agents or formulations specifically designed to circumvent known resistance mechanisms or improve exposure and efficacy in resistant disease.Translation to clinical practice, including early-phase trials, adaptive designs, dose-finding studies, and real-world evidence focused on improving treatment outcomes in resistant or refractory cancers.This Research Topic seeks to advance our understanding of drug resistance in cancer and to support the development of more effective, individualized, and durable therapeutic strategies for patients. Topic editors: Rui Caetano Oliveira, Ahmed M. Elshazly, Dayanidhi Raman Source: https://www.frontiersin.org/research-topics/77648/overcoming-drug-resistance-and-optimizing-cancer-treatment-outcomes