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In situ RAS:RAF binding correlates with response to KRASG12C inhibitors in KRASG12C--mutant non-small cell lung cancer.
Clin Cancer Res
January 2025
Moffitt Cancer Center, Tampa, Florida, United States.
Purpose: Therapeutic efficacy of KRASG12C(OFF) inhibitors (KRASG12Ci) in KRASG12C-mutant non-small cell lung cancer (NSCLC) varies widely. The activation status of RAS signaling in tumors with KRASG12C mutation remains unclear, as its ability to cycle between the active GTP-bound and inactive GDP-bound states may influence downstream pathway activation and therapeutic responses. We hypothesized that the interaction between RAS and its downstream effector RAF in tumors may serve as indicators of RAS activity, rendering NSCLC tumors with a high degree of RAS engagement and downstream effects more responsive to KRASG12Ci compared to tumors with lower RAS---RAF interaction.
View Article and Find Full Text PDFCA-125 as a Biomarker in Renal Medullary Carcinoma: Integrated Molecular Profiling, Functional Characterization, and Prospective Clinical Validation.
Clin Cancer Res
January 2025
The University of Texas MD Anderson Cancer Center, Houston, Texas, United States.
Purpose: Renal medullary carcinoma (RMC) is a highly aggressive malignancy defined by the loss of the SMARCB1 tumor suppressor. It mainly affects young individuals of African descent with sickle cell trait, and it is resistant to conventional therapies used for other renal cell carcinomas. This study aimed to identify potential biomarkers for early detection and disease monitoring of RMC.
View Article and Find Full Text PDFBone-Induced Her2 Promotes Secondary Metastasis in HR+/Her2- Breast Cancer.
Cancer Discov
January 2025
Icahn School of Medicine at Mount Sinai, New York, United States.
Bone metastases can disseminate to secondary sites and promote breast cancer progression creating additional clinical challenges. The mechanisms contributing to secondary metastasis are barely understood. Here, we evaluate the prediction power of Her2-expressing (Her2E) circulating tumor cells (CTCs) after analyzing over 13,000 CTCs from a cohort of 137 metastatic breast cancer (MBC) patients with initial HR+/Her2- status and employ preclinical models of bone metastasis (BM) to validate the role of Her2E CTCs in multi-organ metastases.
View Article and Find Full Text PDFGlutamine, Serine and Glycine at Increasing Concentrations Regulate Cisplatin Sensitivity in Gastric Cancer by Posttranslational Modifications of KDM4A.
Mol Carcinog
January 2025
Department of Gastrointestinal Oncology, Central Laboratory and Precision Medicine Center, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang Province, China.
Gastric cancer is a common digestive system tumor with a high resistance rate that reduces the sensitivity to chemotherapy. Nutrition therapy is an important adjuvant approach to favor the prognosis of gastric cancer. Dietary amino acids contribute greatly to gastric cancer progression by mediating tumor gene expressions, epigenetics, signal transduction, and metabolic remodeling.
View Article and Find Full Text PDFSyngeneic natural killer cell therapy activates dendritic and T cells in metastatic lungs and effectively treats low-burden metastases.
Elife
January 2025
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
Natural killer (NK) cells can control metastasis through cytotoxicity and IFN-γ production independently of T cells in experimental metastasis mouse models. The inverse correlation between NK activity and metastasis incidence supports a critical role for NK cells in human metastatic surveillance. However, autologous NK cell therapy has shown limited benefit in treating patients with metastatic solid tumors.
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