Publications by authors named "R A Depinho"
Pancreatic ductal adenocarcinoma (PDAC) poses a grim prognosis for patients. Recent multidisciplinary research efforts have provided critical insights into its genetics and tumor biology, creating the foundation for rational development of targeted and immune therapies. Here, we review the PDAC genomic landscape and the role of specific oncogenic events in tumor initiation and progression, as well as their contributions to shaping its tumor biology.
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- Advanced pancreatic ductal adenocarcinomas (PDACs) have a poor response to all existing therapies, making effective treatment a significant challenge for patients with late-stage disease.
- Researchers discovered a new chemo-induced signaling network that contributes to chemoresistance in PDAC, highlighting Yap1 in cancer cells and Cox2 in stromal fibroblasts as critical components.
- Co-targeting both Yap1 and Cox2 markedly increased the effectiveness of Gemcitabine treatment in mice, and patient data suggested that combining statins and Cox2 inhibitors with Gemcitabine could enhance survival rates for PDAC patients.
Article Synopsis
- Pancreatic ductal adenocarcinoma (PDAC) is highly resistant to traditional treatments like chemotherapy and radiation, largely due to the influence of oncogenic KRAS, which promotes glucose metabolism and immune suppression in tumors.
- Researchers combined KRAS* inhibitors with immunotherapy agents targeting various immune cells (CXCR1/2 for myeloid cells, anti-LAG3 for T cells, and anti-41BB for dendritic cells) in a mouse model, resulting in significant tumor shrinkage and extended survival for some mice.
- The study demonstrated that this combination therapy improves T cell activity, reduces suppressive myeloid cells, and boosts dendritic cell function in the tumor, suggesting a promising new treatment strategy for
The therapeutic benefit of recently developed mutant KRAS (mKRAS) inhibitors has been limited by the rapid onset of resistance. Here, we aimed to delineate the mechanisms underlying acquired resistance to mKRAS inhibition and identify actionable targets for overcoming this clinical challenge. Previously, we identified Syndecan-1 (SDC1) as a key effector for pancreatic cancer progression whose surface expression is driven by mKRAS.
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