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Inhibition of AHR signaling in pancreatic cancer to increase susceptibility to PD-1/PD-L1 inhibitors and chemotherapy via ELAVL1 pathway
Project promoter: Lithuanian University of Health Sciences
Project title: Inhibition of AHR signaling in pancreatic cancer to increase susceptibility to PD-1/PD-L1 inhibitors and chemotherapy via ELAVL1 pathway
Project code: LT08-1-ŠMSM-K01-002 (Project contract No S-BMT-21-9 (LT08-2-LMT-K-01-041))
Project eligible expenditure: EUR 1000000 (EUR 850000 grant from the EEA Financial Mechanism and EUR 150000 budget co-financing)
Project signature date: 03 December 2020
Project implementation period: 1 January 2021 - 31 December 2023
Project partners:
University of Oslo (NO)
Latvian Institute of Organic Synthesis (LV)
University of Tartu (EE)
Project website
Project summary:
University of Oslo (NO)
Latvian Institute of Organic Synthesis (LV)
University of Tartu (EE)
Project website
Project summary:
The study of incidence and mortality of pancreatic cancer (PC) in Denmark, Finland, Iceland, Norway, and Sweden from 1971 to 2000, suggests that 8 of 1 000 Nordic men and 7 of 1 000 Nordic women will develop PC before the age of 75 years (Acta Oncologica (2007) 46:8, 1064-1069). Study shows that after the mid-1990s the incidence rates for both sexes is increasing and cancer is diagnosed for younger patients (Acta Oncologica (2017) 56:12, 1763-1768). Five-year survival of patients is only 4–5%. Surgery with curative intent remains a treatment of choice; however, it is possible in about 10-20% of all patients. Even after curative surgery most failures occur within 1–2 years of surgery, therefore, there is an increasing need for adjuvant therapy. The median survival of the patients with advanced disease is only about 6 months, and the response to the standard anti-cancer treatment is very limited, thus, it is of a crucial importance to further analyze the pathogenesis of the pancreatic cancer, seek for new improved techniques of early cancer detection, and finally develop new methods of anti-cancer treatment.
Currently existing data suggest that activation of Kyn-AHR-ELAVL1 molecular pathway facilitates tumor progression, helps tumor evade the immune system and/or make tumor cells less susceptible to chemotherapy. We investigate, if the targeted inhibition of this signaling pathway could be used as a new treatment, that slows down the growth and dissemination of malignant cells, restores the cancer suppressing function of the immune cells and increases cancer cell susceptibility to chemotherapy. Thus, the findings of this study could directly impact the outcomes of the treatment of PC patients and allow for more personalized precision medicine application in the future.
Currently existing data suggest that activation of Kyn-AHR-ELAVL1 molecular pathway facilitates tumor progression, helps tumor evade the immune system and/or make tumor cells less susceptible to chemotherapy. We investigate, if the targeted inhibition of this signaling pathway could be used as a new treatment, that slows down the growth and dissemination of malignant cells, restores the cancer suppressing function of the immune cells and increases cancer cell susceptibility to chemotherapy. Thus, the findings of this study could directly impact the outcomes of the treatment of PC patients and allow for more personalized precision medicine application in the future.