TRIAL-based combination therapies in cancers.

ABSTRACT

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) shows promising therapeutic potential in cancer treatment as it is able to trigger extrinsic apoptotic pathways by binding to the cognate death receptor, causing broad-spectrum apoptosis in cancer cells with negligible toxicity to normal cells. However, the majority of cancers display resistance to TRAIL, limiting its clinical utility. Overcoming resistance to TRAIL therapies remains a challenge in the development of effective anti-cancer strategies. To address the limitations of TRAIL therapy, a viable alternative approach involves combining TRAIL with more potent drugs compared to monotherapy. This combination strategy aims to induce synergistic effects or sensitize drug-resistant cancer cells. This review provides an overview of relevant modalities of TRAIL combination therapy, highlighting different drug classes. The findings demonstrate that combining TRAIL with other agents can effectively counteract resistance observed with TRAIL therapies in cancer. These findings lay a foundation for future advancements in TRAIL-based therapies for treating various cancers.