Targeting the NLRP3 Inflammasome as a New Therapeutic Option for Overcoming Cancer

SIMPLE SUMMARY: NLRP3 inflammasome is a cytoplasmic multiprotein complex that assembles in response to cellular distress and promotes maturation and release of the inflammatory cytokines interleukin-1β and IL-18, which contribute to immune responses and inflammation. Aberrant NLRP3 activation has divergent roles in the pathogenesis of inflammation-associated diseases such as cancer, as it can have both protumorigenic and antitumorigenic effects in a context-dependent and tissue-specific manner. Therefore, the fine-tuning of the NLRP3 inflammasome in cancer cells, through a wide range of agents including, such as inhibitors, antagonists and monoclonal antibodies, has been suggested as a viable approach to cancer therapy. ABSTRACT: Inflammasomes are multiprotein complexes that regulate the maturation and secretion of the proinflammatory cytokines interleukin-1beta (IL-1β and interleukin-18 (IL-18) in response to various intracellular stimuli. As a member of the inflammasomes family, NLRP3 is the most studied and best characterized inflammasome and has been shown to be involved in several pathologies. Recent findings have made it increasingly apparent that the NLRP3 inflammasome may also play a central role in tumorigenesis, and it has attracted attention as a potential anticancer therapy target. In this review, we discuss the role of NLRP3 in the development and progression of cancer, offering a detailed summary of NLRP3 inflammasome activation (and inhibition) in the pathogenesis of various forms of cancer. Moreover, we focus on the therapeutic potential of targeting NLRP3 for cancer therapy, emphasizing how understanding NLRP3 inflammasome-dependent cancer mechanisms might guide the development of new drugs that target the inflammatory response of tumor-associated cells.