Pancreatic cancer is a challenging disease to treat, with one of the worse prognoses of any common cancer. Researchers have been actively investigating various therapeutic strategies.
Among these potential targets include newly developed KRAS inhibitors and CDK4/6 inhibitors which target hallmark mutations that are common in pancreatic cancer.
Reprogramming of the PDAC tumor microenvironment with KRAS inhibition
Representative images from syngeneic pancreatic cancer tumor model untreated or treated with the mutant G12D-selective KRAS inhibitor MRTX1133. The abundant deposition of collagen is apparent with commensurate reduction in tumor cellularity. Click to view larger image
While these strategies can slow the growth of the tumor, we believe there is a major opportunity in leveraging the tumor microenvironment and immune system to give rise to more potent therapeutic responses.
The Witkiewicz-Knudsen research team is taking a multi-pronged approach to define critical genetic nodes in pancreatic cancer to directly target the tumor, while understanding the tumor microenvironment and means to unleash anti-tumor immune responses.
See the science
- Kumarasamy V, et al. The extracellular niche and tumor microenvironment enhance KRAS inhibitor efficacy in pancreatic cancer. Cancer Res. 2024 Jan 31. doi: 10.1158/0008-5472.CAN-23-2504.
- Knudsen ES, et al. Targeting dual signalling pathways in concert with immune checkpoints for the treatment of pancreatic cancer. Gut. 2021 Jan;70(1):127-138. doi: 10.1136/gutjnl-2020-321000.
- Weinberg BA, et al. A Phase I Study of Ribociclib Plus Everolimus in Patients with Metastatic Pancreatic Adenocarcinoma Refractory to Chemotherapy. J Pancreat Cancer. 2020 Jun 22;6(1):45-54. doi: 10.1089/pancan.2020.0005.
- Kumarasamy V, et al. Chemotherapy impacts on the cellular response to CDK4/6 inhibition: distinct mechanisms of interaction and efficacy in models of pancreatic cancer. Oncogene. 2020 Feb;39(9):1831-1845. doi: 10.1038/s41388-019-1102-1.
Contact the Witkiewicz-Knudsen Lab
Department of Molecular and Cellular Biology
Roswell Park Comprehensive Cancer Center
Elm and Carlton Streets
Buffalo, NY 14263