This technology is a collection of primary mouse pancreatic ductal adenocarcinoma (PDAC) cells that have developed resistance toward novel pan-RAS-GTP inhibitors, which can be used to test PDAC drugs in vitro and to understand the emergence of resistance to other RAS inhibitors.
Current drugs that are investigated for the treatment of pancreatic ductal adenocarcinoma (PDAC) include agents that target specific RAS proteins, agents that selectively target specific mutant alleles, and agents that bind to RAS proteins selectively in the GDP-bound or GTP-bound states. However, pancreatic tumors frequently develop both intrinsic and acquired resistance to chemotherapy, which can result in the failure of initial therapies and reduce long-term survival. As pan-RAS inhibitors are likely to provoke different mechanisms of resistance than mutant-RAS-selective inhibitors, it is critical to understand how drug resistance emerges to develop new therapeutic strategies to improve patient prognosis, highlighting the need for research tools that exhibit pan-RAS resistance.
This technology encompasses a collection of primary murine pancreatic ductal adenocarcinoma (PDAC) cell lines that have developed resistance against a pan-RAS-GTP inhibitor, along with their matched naive controls. Genetically engineered mice that are prone to develop PDAC were treated with a preclinical variant of a pan-RAS-GTP inhibitor that is soon entering Phase 3 trials. At first, the tumors responded, then later they developed acquired resistance to treatment. New cell lines were isolated from resistant tumors, as well as from mice that never received treatment. The sensitivity of the cell lines to the pan-RAS inhibitor was further tested in vitro and showed that the resistant lines were much less sensitive than the naive controls. Therefore, these cell lines provide a research platform that can aid in the understanding of pan-RAS resistance for drug discovery, as well as subsequent in vitro drug testing. Moreover, as the cell lines were derived from native tumors that developed resistance in vivo on a pure genetic background, these lines are suitable for implantation into an immune-competent host for in vivo testing.
IR CU25070
Licensing Contact: Joan Martinez
