Photodynamic Therapy: Challenges and Innovations for Treating Cancer, Volume II

Photodynamic therapy (PDT) occupies a unique position in the oncology armamentarium — a modality that harnesses the intersection of light, oxygen, and molecular photochemistry to selectively destroy tumor tissue. Despite decades of clinical use across malignancies including skin, head and neck, lung, bladder, and esophageal cancers, PDT continues to be defined as much by its untapped potential as by its established applications.The field is advancing on multiple fronts. The development of next-generation photosensitizers with red- and near-infrared absorption profiles is directly addressing one of PDT’s most persistent limitations: inadequate tissue penetration of activating light. Alongside this, innovations in light delivery — including fiber-optic systems, upconversion nanoparticles, and X-ray-activated photosensitizers — are expanding the anatomical reach of PDT to deep-seated and previously inaccessible tumors. Strategies to overcome tumor hypoxia, a critical determinant of Type II PDT efficacy, are gaining momentum, including the emergence of Type I photosensitizers that operate through oxygen-independent radical pathways.Nanotechnology is playing an increasingly central role in PDT optimization. Advanced nanocarrier platforms — including liposomes, polymeric nanoparticles, metal-organic frameworks, and self-assembling supramolecular systems — are enabling cell-specific targeting, stimuli-responsive photosensitizer release, and improved pharmacokinetic profiles. These systems are also facilitating the co-delivery of complementary therapeutic agents, supporting rationally designed combination strategies.The immunological dimension of PDT has emerged as one of the most compelling areas of current investigation. PDT-induced immunogenic cell death, damage-associated molecular pattern release, and tumor microenvironment reprogramming are opening new avenues for synergy with immune checkpoint inhibitors and cancer vaccines. Understanding how PDT reshapes the immunosuppressive tumor microenvironment — and how to leverage this therapeutically — is a rapidly evolving priority.Translational momentum is building. Novel PDT agents and protocols are advancing through preclinical and early clinical evaluation, and image-guided PDT approaches are improving treatment precision and real-time monitoring. The integration of PDT into multimodal treatment frameworks — alongside chemotherapy, radiotherapy, and immunotherapy — represents a frontier of both scientific and clinical importance.This Research Topic invites contributions spanning the mechanistic, translational, and clinical dimensions of PDT in oncology. Sub-themes include, but are not limited to:• Mechanistic studies of PDT-induced cell death, including immunogenic cell death and tumor microenvironment modulation• New molecular and cellular therapeutic targets for PDT• Advanced nanocarriers for cell-specific or stimuli-responsive photosensitizer delivery• Type I and oxygen-independent photosensitizers for hypoxic tumor environments• Translational and clinical research on novel PDT agents and protocols• Combination strategies of PDT with chemo-, immuno-, or radiotherapy• Innovative approaches to improve light penetration depth, including upconversion nanoparticles and X-ray activation• Image-guided and theranostic PDT platformsManuscripts based solely on bioinformatics, computational analysis, or public database predictions without independent cohort or biological validation (in vitro/in vivo) will not be accepted in any section of Frontiers in Oncology. Topic editors: CRISTINA PACHECO-SOARES, Shiv K Gupta, Ravi Prakash Sahu, Juliana Ferreira-Strixino Source: https://www.frontiersin.org/research-topics/82507/photodynamic-therapy-challenges-and-innovations-for-treating-cancer-volume-ii