Absent in melanoma 2 (AIM2) is a member of the innate immune sensors that recognizes cytosolic nucleic acids, leading to inflammasome assembly. In recent years, several studies in the oncology field have highlighted the presence of cytoplasmic double-stranded DNA (dsDNA) following necrosis and/or genomic instability, which is typical of malignant transformation. The recognition of dsDNA by the AIM2 inflammasome either in cancer cells or in immune cells can further exacerbate inflammatory processes on the basis of cancer progression. In this context, the role of AIM2 in cancer is still controversial in that some authors assume that AIM2 activation has pro-tumor activities, while others define it as anti-tumor. This discrepancy may be due to the nature of the cells where AIM2 is expressed or the histology of the tumor. This review aims to provide an overview of the controversial role of AIM2 in cancer, taking into consideration the pharmacological tools currently available to modulate AIM2 activity in cancer.

The link between inflammation and cancer has been extensively studied over the years. While the inflammatory process can facilitate tumor establishment and progression, on the other hand, current clinical approaches aim to boost the immune system against the tumor mass. In this scenario, the conventional chemotherapy has proven to induce immunogenic cell death in that the release of danger-associated alarmins can foster the cytotoxic immunity following the blockade of immune checkpoints. The release of alarmins can activate the inflammasome pathway. Thus, one of the questions is as follows: can conventional anti-tumor drugs lead to inflammasome activation? And if so, is the resulting effect anti- or pro-tumor? In this review, we provide an overview on the role of the inflammasome in cancer.