5-ALA in Oncology: Current Clinical Applications, Biological Limitations, and Emerging Translational Strategies.

5-Aminolevulinic acid (5-ALA) has emerged as an important theranostic agent in oncology due to its selective intracellular conversion to protoporphyrin IX (PpIX), enabling both photodynamic diagnosis (PDD) and photodynamic therapy (PDT). This narrative review summarizes current knowledge regarding the biological mechanisms underlying 5-ALA metabolism, selective tumor accumulation, and the clinical applications of 5-ALA-based approaches across multiple oncological indications. Particular emphasis is placed on glioblastoma, head and neck lesions, dermatological malignancies, urological cancers, gynecological lesions, and emerging translational applications. The review also discusses key biological and technical limitations, including tumor hypoxia, restricted light penetration, heterogeneous PpIX accumulation, resistance mechanisms, and tumor-specific variability. Recent advances in drug delivery systems, nanotechnology, sonodynamic therapy, radiodynamic strategies, and combination immunotherapeutic approaches are also highlighted. Collectively, current evidence indicates that while 5-ALA has established clinical utility in selected indications, many applications remain preclinical or early translational, underscoring the need for further well-designed clinical studies.