Yuanfu Qi

Inflammasome activation and pyroptosis are central to innate immune responses and play either protective or detrimental roles in host defense. Inhibiting these processes holds significant therapeutic promise for diseases exacerbated by inflammasome activation. However, clinically targeting this pathway remains challenging, as blocking pyroptosis may trigger alternative cell death pathways. In this mini-review, we summarize bacterial and viral infections in which inflammasome activation and pyroptosis are detrimental to host defense, explore the mechanisms underlying cell death switching, and discuss how effectively blocking multiple cell death pathways and potential interconversions represents a key consideration for current intervention strategies.

Breast cancer ranks as one of the most common malignancies among women, with its prognosis and therapeutic efficacy heavily influenced by factors associated with the tumor cell biology, particularly the tumor microenvironment (TME). The diverse elements of the TME are engaged in dynamic bidirectional signaling interactions with various pathways, which together dictate the growth, invasiveness, and metastatic potential of breast cancer. The Hedgehog (Hh) signaling pathway, first identified in Drosophila, has been established as playing a critical role in human development and disease. Notably, the dysregulation of the Hh pathway is recognized as a major driver in the initiation, progression, and metastasis of breast cancer. Consequently, elucidating the mechanisms by which the Hh pathway interacts with the distinct components of the breast cancer TME is essential for comprehensively evaluating the link between Hh pathway activation and breast cancer risk. This understanding is also imperative for devising novel targeted therapeutic strategies and preventive measures against breast cancer. In this review, we delineate the current understanding of the impact of Hh pathway perturbations on the breast cancer TME, including the intricate and complex network of intersecting signaling cascades. Additionally, we focus on the therapeutic promise and clinical challenges of Hh pathway inhibitors that target the TME, providing insights into their potential clinical utility and the obstacles that must be overcome to harness their full therapeutic potential.