The Role of TRAIL Signaling in Cancer: Searching for New Therapeutic Strategies

Simple Summary In the realm of modern medicine, the battle against cancer is a relentless pursuit that demands continuous innovation. Among the numerous elements in the complex world of cancer biology, TRAIL has emerged as a focal point for researchers and clinicians alike. Its diverse role in cancer, especially its influence on the tumor microenvironment (TME), has sparked extensive research. This article explores the intricacies of TRAIL's function in cancer, revealing its dual nature-capable of both inhibiting and, conversely, promoting, cancer growth. TRAIL impacts a wide array of processes, from apoptosis to modulation of the immune response, and plays a crucial part in tumor initiation, progression, and invasion. Moving forward, the potential of TRAIL as a transformative element in cancer therapy is gaining recognition. New therapeutic approaches, including combination therapies, immunotherapies, and gene delivery methods, are being developed to leverage TRAIL's potential for the benefit of cancer patients. Moreover, as our understanding of the TME and its effects on TRAIL's efficacy grows, it is opening doors to more targeted and effective treatment strategies.Abstract Cancer continues to pose a significant threat to global health, with its status as a leading cause of death remaining unchallenged. Within the realm of cancer research, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) stands out as a critical player, having been identified in the 1990s as the tenth member of the TNF family. This review examines the pivotal role of TRAIL in cancer biology, focusing on its ability to induce apoptosis in malignant cells through both endogenous and exogenous pathways. We provide an in-depth analysis of TRAIL's intracellular signaling and intercellular communication, underscoring its potential as a selective anticancer agent. Additionally, the review explores TRAIL's capacity to reshape the tumor microenvironment, thereby influencing cancer progression and response to therapy. With an eye towards future developments, we discuss the prospects of harnessing TRAIL's capabilities for the creation of tailored, precision-based cancer treatments, aiming to enhance efficacy and improve patient survival rates.