Publications by authors named "Max Quinn"
Objectives: We designed this study to test whether clazakizumab, a direct interleukin-6 inhibitor, benefits patients hospitalized with severe or critical COVID-19 disease accompanied by hyperinflammation.
Design: Multicenter, randomized, double-blinded, placebo-controlled, seamless phase II/III trial.
Setting: Five U.
Cyclin-dependent kinase 7 (CDK7) is a central regulator of the cell cycle and gene transcription. However, little is known about its impact on genomic instability and cancer immunity. Using a selective CDK7 inhibitor, YKL-5-124, we demonstrated that CDK7 inhibition predominately disrupts cell-cycle progression and induces DNA replication stress and genome instability in small cell lung cancer (SCLC) while simultaneously triggering immune-response signaling.
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- Mutations in the KRAS gene are found in about 30% of lung adenocarcinomas, making treatment challenging due to tumor resistance and immunosuppressive factors.
- Recent studies show that combining BET bromodomain inhibitors, like JQ1, with PD-1 antibodies can enhance the immune response against tumors by reducing regulatory T cells and activating T cells more effectively.
- This combination therapy resulted in significant and lasting antitumor effects in mouse models, suggesting a potential new treatment strategy for lung adenocarcinoma and other solid tumors.
Article Synopsis
- 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
- * Researchers conducted a synthetic lethal screen that revealed HDAC6 as a promising target when paired with the BET inhibitor JQ1, hinting at a new treatment approach.
- * The combination of the HDAC6 inhibitor ricolinostat and JQ1 significantly reduced tumor growth, with evidence showing that NK cells are crucial for the effectiveness of this combined treatment.
(or ) aberrations, including both amplification and mutations, have been classified as oncogenic drivers that contribute to 2% to 6% of lung adenocarcinomas. amplification is also an important mechanism for acquired resistance to EGFR tyrosine kinase inhibitors (TKI). However, due to limited preclinical studies and clinical trials, currently there is still no available standard of care for lung cancer patients with aberrations.
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- 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.
systems that incorporate features of the tumor microenvironment and model the dynamic response to immune checkpoint blockade (ICB) may facilitate efforts in precision immuno-oncology and the development of effective combination therapies. Here, we demonstrate the ability to interrogate response to ICB using murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS). MDOTS/PDOTS isolated from mouse and human tumors retain autologous lymphoid and myeloid cell populations and respond to ICB in short-term three-dimensional microfluidic culture.
View Article and Find Full Text PDFCells 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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