AI Article Synopsis
- Activation of the Axl receptor tyrosine kinase in pancreatic cancer (PDAC) leads to worse patient outcomes by promoting immune evasion and resistance to treatments like gemcitabine.
- The selective Axl inhibitor BGB324 helps improve gemcitabine's effectiveness and reduces aggressive features of PDAC by targeting the tumor-immune interface and altering immune responses.
- Research findings suggest that Axl inhibitors could be clinically developed to enhance treatment strategies for pancreatic cancer patients, as they promote better tumor differentiation and immune stimulation.
Article Abstract
Activation of the receptor tyrosine kinase Axl is associated with poor outcomes in pancreatic cancer (PDAC), where it coordinately mediates immune evasion and drug resistance. Here, we demonstrate that the selective Axl kinase inhibitor BGB324 targets the tumor-immune interface to blunt the aggressive traits of PDAC cells and enhance gemcitibine efficacy Axl signaling stimulates the TBK1-NFκB pathway and innate immune suppression in the tumor microenvironment. In tumor cells, BGB324 treatment drove epithelial differentiation, expression of nucleoside transporters affecting gemcitabine response, and an immune stimulatory microenvironment. Our results establish a preclinical mechanistic rationale for the clinical development of Axl inhibitors to improve the treatment of PDAC patients. These results establish a preclinical mechanistic rationale for the clinical development of AXL inhibitors to improve the treatment of PDAC patients. .
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754222 | PMC |
| http://dx.doi.org/10.1158/0008-5472.CAN-17-1973 | DOI Listing |
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