The LKB1 (also called STK11) tumor suppressor is mutationally inactivated in ∼20% of non-small cell lung cancers (NSCLC). LKB1 is the major upstream kinase activating the energy-sensing kinase AMPK, making LKB1-deficient cells unable to appropriately sense metabolic stress. We tested the therapeutic potential of metabolic drugs in NSCLC and identified phenformin, a mitochondrial inhibitor and analog of the diabetes therapeutic metformin, as selectively inducing apoptosis in LKB1-deficient NSCLC cells. Therapeutic trials in Kras-dependent mouse models of NSCLC revealed that tumors with Kras and Lkb1 mutations, but not those with Kras and p53 mutations, showed selective response to phenformin as a single agent, resulting in prolonged survival. This study suggests phenformin as a cancer metabolism-based therapeutic to selectively target LKB1-deficient tumors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579627 | PMC |
| http://dx.doi.org/10.1016/j.ccr.2012.12.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Explainable Machine Learning to Predict Treatment Response in Advanced Non-Small Cell Lung Cancer.
JCO Clin Cancer Inform
January 2025
Emory University School of Medicine, Atlanta, GA.
Purpose: Immune checkpoint inhibitors (ICIs) have demonstrated promise in the treatment of various cancers. Single-drug ICI therapy (immuno-oncology [IO] monotherapy) that targets PD-L1 is the standard of care in patients with advanced non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50%. We sought to find out if a machine learning (ML) algorithm can perform better as a predictive biomarker than PD-L1 alone.
View Article and Find Full Text PDFOccult metastases and survival of lung cancer by clinical diagnosis and CT screening: A simulation study.
PLoS One
January 2025
Department of Medicine Epidemiology and Population Sciences, Baylor College of Medicine, Houston, Texas, United States of America.
Objectives: It is significant to know how much early detection and screening could reduce the proportion of occult metastases and benefit NSCLC patients.
Methods: We used previously designed and validated mathematical models to obtain the characteristics of LC in the population including undetectable metastases at the time of diagnosis. The survival was simulated using the survival functions from Surveillance, Epidemiology and End Results (SEER) data stratified by stage.
Therapeutic effect of fully human anti-Nrp-1 antibody on non-small cell lung cancer in vivo and in vitro.
Cancer Immunol Immunother
January 2025
Public Center of Experimental Technology, The School of Basic Medical Sciences, Southwest Medical University, Luzhou, 646000, Sichuan Province, China.
Although immune checkpoint inhibitors have changed the treatment paradigm for non-small cell lung cancer (NSCLC), not all patients benefit from them. Therefore, there is an urgent need to explore novel immune checkpoint inhibitors. Neuropilin-1 (Nrp-1) is a unique immune checkpoint capable of exerting antitumor effects through CD8 T cells.
View Article and Find Full Text PDFEfficacy and safety of PD-1 blockade-activated neoantigen specific cellular therapy for advanced relapsed non-small cell lung cancer.
Cancer Immunol Immunother
January 2025
Department of Oncology, Lianyungang Clinical College of Nanjing Medical University/The First People's Hospital of Lianyungang, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222002, China.
Background: Due to its strong immunogenicity and tumor specificity, neoplastic antigen has emerged as an immunotherapy target with wide therapeutic prospect and clinical application value. Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor immunity. So, we conducted single-arm trial to assess the safety and efficacy of PD-1 blockade(Camrelizumab)-activated neoantigen specific cellular therapy (aNASCT) on advanced relapsed non-small lung cancer(NSCLC)(ClinicalTrials.
View Article and Find Full Text PDFHigh CD38 expression defines a mitochondrial function-adapted CD8 T cell subset with implications for lung cancer immunotherapy.
Cancer Immunol Immunother
January 2025
Department of Respiratory and Critical Medicine, the First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, China.
Despite identifying specific CD8 T cell subsets associated with immunotherapy resistance, the molecular pathways driving this process remain elusive. Given the potential role of CD38 in regulating CD8 T cell function, we aimed to investigate the accumulation of CD38CD8 T cells in lung cancer and explore its role in immunotherapy resistance. Phenotypic analysis of tumoral CD8 T cells from both lung cancer patients and immunotherapy-resistant preclinical models revealed that CD38-expressing CD8 T cells consist of CD38 and CD38 subsets.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!