Pyroptosis and the fight against lung cancer

• Published in: Medicinal research reviews 2025-01, Vol.45 (1), p.5-28
• Main Authors: Wang, Jiwei, Su, Huiling, Wang, Min, Ward, Richard, An, Su, Xu, Tian‐Rui
• Format: Article
• Language: English
• Subjects: Animals; antitumor immunity; Cancer therapies; gasdermins; Humans; inflammasome; Inflammasomes - metabolism; Lung cancer; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Pyroptosis; Signal Transduction
• ISSN: 0198-6325; 1098-1128; 1098-1128
• DOI: 10.1002/med.22071

Pyroptosis, a newly characterized type of inflammatory programmed cell death (PCD), is usually triggered by multiple inflammasomes which can recognize different danger or damage‐associated molecular patterns (DAMPs), leading to the activation of caspase‐1 and the cleavage of gasdermin D (GSDMD). Gasdermin family pore‐forming proteins are the executers of pyroptosis and are normally maintained in an inactive state through auto‐inhibition. Upon caspases mediated cleavage of gasdermins, the pro‐pyroptotic N‐terminal fragment is released from the auto‐inhibition of C‐terminal fragment and oligomerizes, forming pores in the plasma membrane. This results in the secretion of interleukin (IL)‐1β, IL‐18, and high‐mobility group box 1 (HMGB1), generating osmotic swelling and lysis. Current therapeutic approaches including chemotherapy, radiotherapy, molecularly targeted therapy and immunotherapy for lung cancer treatment efficiently force the cancer cells to undergo pyroptosis, which then generates local and systemic antitumor immunity. Thus, pyroptosis is recognized as a new therapeutic regimen for the treatment of lung cancer. In this review, we briefly describe the signaling pathways involved in pyroptosis, and endeavor to discuss the antitumor effects of pyroptosis and its potential application in lung cancer therapy, focusing on the contribution of pyroptosis to microenvironmental reprogramming and evocation of antitumor immune response.