Molecular basis of chemosensitivity

Chemosensitivity — the degree to which cancer cells respond to therapeutic agents — remains one of the central determinants of treatment success in oncology. Despite substantial advances in drug development, variability in patient response, acquired resistance, and dose-limiting toxicity continue to undermine the clinical efficacy of both conventional chemotherapy and targeted agents. Understanding the molecular mechanisms that govern how tumor cells sense, process, and respond to cytotoxic and targeted therapies is essential for improving treatment outcomes and minimizing adverse effects.

This Research Topic aims to bring together original research, reviews, and perspective articles that explore the molecular and cellular basis of chemosensitivity across different cancer types and therapeutic modalities. We welcome contributions addressing, but not limited to, the following subtopics:

• Molecular mechanisms of chemotherapy-induced toxicity: Studies examining the cellular and molecular pathways underlying off-target and dose-limiting toxicities of chemotherapeutic agents, including but not limited to oxidative stress, DNA damage response, mitochondrial dysfunction, and inflammatory signaling. Contributions addressing biomarkers predictive of toxicity, as well as strategies to mitigate adverse effects while preserving therapeutic efficacy, are especially encouraged.

• Targeted anti-cancer treatment and combined chemo-immunotherapy: Research exploring the mechanisms of action, resistance, and synergy of targeted therapies (small molecules, antibody-drug conjugates, kinase inhibitors) alone or in combination with immunotherapeutic approaches. This includes studies on tumor microenvironment modulation, immune checkpoint interactions, and rational combination strategies designed to enhance chemosensitivity and overcome resistance.

We encourage submissions employing a range of methodologies — from in vitro and in vivo mechanistic studies to translational and clinical investigations — that advance our understanding of how molecular determinants shape therapeutic response. Articles integrating multi-omics approaches, biomarker discovery, and mechanistic insight into drug resistance and sensitivity are particularly welcome.

By consolidating current knowledge and emerging discoveries in this field, this Research Topic seeks to provide a valuable resource for researchers and clinicians working toward more effective, safer, and personalized cancer treatment strategies.