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PROTAC-based synthetic lethality strategy endogenously activates systemic STING to boost antitumor immunity - PubMed

3 hours ago
  • #antitumor immunity
  • #PROTAC
  • #STING pathway
  • PROTAC-based synthetic lethality strategy activates STING pathway to enhance antitumor immunity.
  • Degradation of PARP1 and BRD4 disrupts DNA repair, leading to cytosolic DNA leakage and STING activation.
  • Superior antitumor efficacy observed in multiple tumor models with robust CD8+ T cell and NK cell responses.
  • Strategy suppresses pulmonary metastasis progression by leveraging cGAS-STING-mediated innate immunity.
  • Integration of synthetic lethality with immunogenic stress response offers a new paradigm for cancer therapy.