Comprehensive Review on How Repurposed Drugs Modulate Antitumor Immunity: Harnessing Damage-Associated Molecular Patterns

Abstract

Recent research has significantly altered the understanding of the immunogenic profile of certain processes of cancer cell death, leading to the recognition of a new subclass of apoptosis called “immunogenic apoptosis.” This form of cell death, induced by specific chemotherapeutic agents, has been shown to elicit a “chemotherapy vaccine effect” in vivo, effectively stimulating an antitumor immune response. At the molecular level, “a collection of molecules” known as “damage-associated molecular patterns (DAMPs)” have been identified as key contributors to the immunogenicity of various cell death pathways. Intracellular molecules, such as heat-shock proteins, high-mobility group box 1 protein, and calreticulin, act as DAMPs when exposed or secreted in response to specific certain stressors, stimuli, and modes of cell death. These discoveries have fueled ongoing research focused on the identification of novel DAMPs, uncovering new mechanisms of their exposure or secretion and developing therapeutic agents capable of inducing immunogenic cell death (ICD). In addition, there is growing interest in addressing the current challenges and limitations within this emerging paradigm. The authors believe that this integrated strategy—combining DAMPs, ICD, and anticancer therapies—may hold the key to significantly reducing cancer-related mortality in the near future.