Publications by authors named "Ashley A Merlino"
Despite extensive efforts, oncogenic KRAS remains resistant to targeted therapy. Combined downstream RAL-TBK1 and MEK inhibition induces only transient lung tumor shrinkage in KRAS-driven genetically engineered mouse models (GEMMs). Using the sensitive KRAS;LKB1 (KL) mutant background, we identify YAP1 upregulation and a therapy-induced secretome as mediators of acquired resistance.
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- Some agents targeting downstream signaling pathways, like MEK inhibitors, are being developed to address the challenges of directly targeting mutant KRAS in lung cancer, but their effectiveness in combination with chemotherapy is still debated.
- A new genetically engineered mouse model mimicking the most common KRAS mutation in lung cancer shows that KRAS tumors respond better to treatment with selumetinib, a MEK inhibitor, compared to other tumor types.
- The study reveals that the presence of mutations in tumor-suppressor genes, like p53, affects the sensitivity of KRAS lung tumors to treatments, suggesting that specific genetic profiles should guide therapy options for lung cancer patients.
Article Synopsis
- Immune checkpoint blockade, like PD-1 receptor antibodies, can lead to significant tumor reductions, but researchers are looking for ways to boost their effectiveness.
- A study found that using small-molecule inhibitors of CDK4/6 can enhance T-cell activation and tumor response, even while reducing overall T-cell proliferation.
- The findings suggest that combining CDK4/6 inhibitors with existing immunotherapy treatments could improve cancer treatment outcomes, emphasizing the need for innovative strategies to augment immunotherapy efficacy.
Cells lacking the tumor suppressor gene alter their metabolism to match the demands of accelerated growth, leaving them highly vulnerable to stress. However, targeted therapy for LKB1-deficient cancers has yet to be reported. In both cell lines and a genetically engineered mouse model of -induced lung cancer, much higher rates of DNA damage occur, resulting in increased dependence on Chk1 checkpoint function.
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