Combinatorial Strategies in Radiotherapy to Enhance Radiosensitivity and Antitumor Immunity

Radiotherapy remains a cornerstone of cancer treatment, yet intrinsic radioresistance, tumor heterogeneity, and dose-limiting normal tissue toxicity continue to constrain therapeutic outcomes. While conventional approaches have focused on optimizing physical dose delivery, a new frontier is emerging: the integration of biological, technological, and physical modalities designed to enhance radiosensitivity at the tumor level. Advances in nanotechnology, bioelectric therapies, targeted radiosensitizers, and imaging-guided adaptation are opening novel avenues to overcome radioresistance and improve the therapeutic ratio, priorities that will define the next generation of precision radiation oncology.

This Research Topic seeks to advance the field by exploring innovative strategies that enhance radiotherapy efficacy beyond traditional paradigms. We aim to bridge the gap between emerging technologies, including nanoparticle-based radiosensitizers, pulsed electric fields, and novel drug delivery platforms, and their biological and clinical integration. A key objective is to examine how these approaches modulate the DNA damage response, tumor vasculature, hypoxic microenvironment, and treatment resistance pathways. We also encourage contributions on imaging-driven personalization and predictive biomarkers, which are essential for translating these advances into adaptive, patient-specific treatment strategies.

We welcome original research, reviews, perspectives, and brief reports addressing, but not limited to, the following themes:
• Nanoparticle-based radiosensitizers and targeted drug delivery platforms.
• Physical and device-based technologies, including electroporation, pulsed electric fields, and focused ultrasound.
• DNA damage response modulation and repair pathway inhibition as radiosensitizing strategies.
• Tumor microenvironment and vascular modifiers that enhance radiation response.
• Hypoxia-targeting approaches and oxygen enhancement strategies.
• Imaging-guided treatment adaptation, dose painting, and functional response assessment.
• Biomarkers predicting radiosensitivity, treatment resistance, or normal tissue toxicity.
• Optimization of timing, sequencing, and dose interactions in multimodal regimens.
• Immune signaling crosstalk arising from radiosensitization strategies.
• Preclinical models and early-phase clinical studies evaluating novel radiosensitization approaches.
• Translational challenges, workflow integration, and regulatory considerations.

Submissions should provide mechanistic insights, translational findings, or clinical correlations and may involve in vitro, in vivo, or patient-derived data. We particularly welcome multidisciplinary contributions that connect technological innovation with biological mechanisms and clinical endpoints. Together, these studies will inform the development of more effective, personalized radiotherapy strategies and accelerate the translation of emerging radiosensitization technologies into clinical practice.

Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal.

Topic Coordinator Barath Udayasuryan is employed by Genentech. All other Topic Editors declare no competing interests with regard to the Research Topic subject.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Radiosensitization, Radiotherapy, Nanoparticle Radiosensitizers, DNA Damage Response, Pulsed Electric Fields, Tumor Microenvironment, Imaging-Guided Radiotherapy, Predictive Biomarkers, Drug Delivery Platforms, Clinical Translation

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.