Sotorasib is a first-in-class small molecule that irreversibly inhibits KRAS G12C, locking it in an inactive state, inhibiting oncogenic signaling, and inducing a proinflammatory microenvironment. Here, we report the first case of life-threatening hepatitis in a patient with NSCLC shortly after commencing sotorasib, in which biopsy result was consistent with checkpoint inhibitor (CPI) immune-related adverse event, implicating sotorasib as being able to trigger CPI immune hepatitis. Given the large proportion of patients potentially treatable with sequential sotorasib after CPI, coupled with limited trial data, sotorasib-triggered CPI immune-related hepatitis should be considered in patients with sotorasib hepatotoxicity.
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http://dx.doi.org/10.1016/j.jtocrr.2021.100213 | DOI Listing |
Discov Oncol
January 2025
Department of Respiratory Medicine, The First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), 1882 South Zhonghuan Road, Jiaxing, 314000, Zhejiang, China.
Objective: The purpose of this study is to analyze the predictive value of neutrophil to lymphocyte ratio (NLR), lymphocyte count to monocyte count ratio (LMR), platelet to lymphocyte ratio (PLR), platelet count multiplied by neutrophil count to lymphocyte count ratio (SII), red blood cell distribution width (RDW), packed cell volume (PCV), and plateletcrit (PCT) levels in advanced non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 inhibitors.
Materials And Methods: From March 2019 to August 2023, we screened 104 of 153 patients with stage III unresectable local advanced NSCLC and IV NSCLC who received PD-1/PD-L1 inhibitor therapy at our hospital and met the inclusion and exclusion criteria for analysis. All patients were collected for clinical information, including baseline blood indicator (NLR, PLR, LMR, SII, CRP, RDW, PCV and PCT) levels before PD-1/PD-L1 inhibitor therapy and blood indicator levels and imaging evaluation results every two cycles after PD-1/PD-L1 inhibitor therapy.
NPJ Precis Oncol
January 2025
Zentalis Pharmaceuticals, Inc., San Diego, CA, USA.
Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.
View Article and Find Full Text PDFJ Hematol Oncol
January 2025
Department of Radiation Oncology, Henan Provincial Key Laboratory of Radiation Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People's Republic of China.
Background: Targeting glucose uptake by glucose transporter (GLUT) inhibitors is a therapeutic opportunity, but efforts on GLUT inhibitors have not been successful in the clinic and the underlying mechanism remains unclear. We aim to identify the key metabolic changes responsible for cancer cell survival from glucose limitation and elucidate its mechanism.
Methods: The level of phosphorylated YAP was analyzed with Western blotting and Phos-tag immunoblotting.
J Immunother Cancer
January 2025
Center for Translational Research in Hematologic Malignancies, Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, Texas, USA
Background: Cancer immunotherapy using immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, patients with multiple myeloma (MM) rarely respond to ICB. Accumulating evidence indicates that the complicated tumor microenvironment (TME) significantly impacts the efficacy of ICB therapy.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Background: Immune checkpoint inhibitors (ICIs) in combination with antiangiogenic drugs have shown promising outcomes in the third-line and subsequent treatments of patients with microsatellite stable metastatic colorectal cancer (MSS-mCRC). Radiotherapy (RT) may enhance the antitumor effect of immunotherapy. However, the effect of RT exposure on patients receiving ICIs and targeted therapy remains unclear.
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