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Methods of Treating Cancers Using STING Agonists

STING agonists reprogram the immune system from being tumor-prone to tumor-defying, which can be exploited for cancer treatment.

  • Therapeutics

Project Overview

  • The introduction of PARP inhibitors (PARPi) has transformed the treatment of ovarian cancer and to a lesser extent of breast cancer patients with BRCA1/2 inactivating mutations.
  • The introduction of EGFR tyrosine kinase inhibitors (EGFR-TKI) has revolutionized the treatment landscape of lung cancer patients with EGFR mutations. However, not all patients respond to PARPi and EGFR-TKI, or tumors become resistant to these two drugs, which are common in the clinic.
  • Researchers at Dana-Farber have found that in PARPi or EGFR-TKI resistant tumors, a STING agonist triggered an increase of tumor-infiltrating T cells which enabled PARPi or EGFR-TKI functionality.

Technology

The discovery that a STING agonist reprograms the immune system from being tumor-prone to tumor-defying can be exploited for cancer treatment beyond the combination with PAPRi or EGFR-TKI.  The use of a STING agonist to prevent or overcome drug resistance. This can be in combination with a PARPi, an EGFR-TKI, or a DNA synthesis inhibitor.

Further Details:

  • Targeting tumor-associated macrophages with STING agonism improves the antitumor efficacy of osimertinib in a mouse model of EGFR-mutant lung cancer, Zhao and Lin et al. Front. Immunol. 2023, 14:1077203, DOI: 10.3389/fimmu.2023.1077203 
  • STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer, Zhao and Wang et al. Nat. Comm. 2022, 13, DOI: 10.1038/s41467-022-30568-1 
  • STING agonism overcomes STAT3-mediated immunosuppression and adaptive resistance to PARP inhibition in ovarian cancer, Zhao and Ding et al. J Immunother Cancer. 2023, 11: e005627, DOI: 10.1136/jitc-2022-005627 

Team Members: Jean Zhao, PhD, Qiwei Wang, PhD, Liya Ding, PhD

Applications

  • Patients with ovarian cancer that do not respond any longer to PARPi 
  • Patients with BRCA1/2 mutated breast cancer that no longer respond to PARPi 
  • Patients with EGFR-mutated lung cancer that no longer respond to EGFR-TKI 
  • To overcome drug resistance characterized by the activation of STAT3 

Opportunities

Dana-Farber is seeking a non-exclusive license or sponsored research.

Get in touch

Team Members

Jean Zhao, PhD

Investigator, Cancer Biology and Signal Transduction, Dana-Farber

Professor, Harvard Medical School