Periodic Reporting for period 1 - DIM-CrIC (Decreasing Pancreatic Adenocarcinoma-related Inflammation using small molecule inhibitors of STING)
Reporting period: 2020-06-01 to 2021-11-30
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors. Contrary to several major cancer types for which significant progress has been made in recent years, PDAC is projected to become the second leading cause of cancer-related death within the next two decades. In particular, PDAC is highly refractory to single-agent immunotherapy and likely necessitates additional immuno-stimulation to allow efficient targeting. On the other hand, persistent inflammation in PDAC, as in additional cancers, is a well-established aggravating factor that ultimately promotes immune exhaustion and immunosuppression. Therefore, the care of PDAC patients presents high unmet needs and major space for improvement.
The DIM-CrIC project aimed to develop and test a treatment for PDAC. We in particular focused on the design of therapeutic approaches that allow the reactivation of PDAC immunogenicity. To this aim, we in targeted a pathway that has been involved in promoting tumor-associated inflammation, that in turn can skew immune responses towards anti-tumor or tolerigenic responses. By pursuing this aim, the DIM-CrIC project has brought two major scientific outputs:
(i) we identified that inhibiting this pathway that controls inflammatory responses in the PDAC tumor microenvironment allowed tumor clearance and promoted tumor-specific immune responses while allowing the expression or markers that predict response to immunotherapy and,
(ii) we identified a drug that potentiates the activity of drugs that activate tumor-associated inflammatory responses and therapeutic combinations that potentiate the activity of molecules known to promote responses to immunotherapy.
Therefore, the DIM-CrIC project has identified potential novel means to tackle STING-dependent inflammation in PDAC. The use of the findings made in the course of the project have been patented. Exploitation of the data obtained in the course of DIM-CrIC should pave the way towards evaluation of whether the proposed therapeutic combinations effectively potentiate response to immunotherapy. This work has therefore contributed to the global effort to unravel novel routes to harness cancer-related inflammation to the benefit of patients.
The DIM-CrIC project aimed to develop and test a treatment for PDAC. We in particular focused on the design of therapeutic approaches that allow the reactivation of PDAC immunogenicity. To this aim, we in targeted a pathway that has been involved in promoting tumor-associated inflammation, that in turn can skew immune responses towards anti-tumor or tolerigenic responses. By pursuing this aim, the DIM-CrIC project has brought two major scientific outputs:
(i) we identified that inhibiting this pathway that controls inflammatory responses in the PDAC tumor microenvironment allowed tumor clearance and promoted tumor-specific immune responses while allowing the expression or markers that predict response to immunotherapy and,
(ii) we identified a drug that potentiates the activity of drugs that activate tumor-associated inflammatory responses and therapeutic combinations that potentiate the activity of molecules known to promote responses to immunotherapy.
Therefore, the DIM-CrIC project has identified potential novel means to tackle STING-dependent inflammation in PDAC. The use of the findings made in the course of the project have been patented. Exploitation of the data obtained in the course of DIM-CrIC should pave the way towards evaluation of whether the proposed therapeutic combinations effectively potentiate response to immunotherapy. This work has therefore contributed to the global effort to unravel novel routes to harness cancer-related inflammation to the benefit of patients.