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Elucidation of the mutational landscape of human cancer has progressed rapidly and been accompanied by the development of therapeutics targeting mutant oncogenes. However, a comprehensive mapping of cancer dependencies has lagged behind and the discovery of therapeutic targets for counteracting tumor suppressor gene loss is needed. To identify vulnerabilities relevant to specific cancer subtypes, we conducted a large-scale RNAi screen in which viability effects of mRNA knockdown were assessed for 7,837 genes using an average of 20 shRNAs per gene in 398 cancer cell lines. We describe findings of this screen, outlining the classes of cancer dependency genes and their relationships to genetic, expression, and lineage features. In addition, we describe robust gene-interaction networks recapitulating both protein complexes and functional cooperation among complexes and pathways. This dataset along with a web portal is provided to the community to assist in the discovery and translation of new therapeutic approaches for cancer.
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http://dx.doi.org/10.1016/j.cell.2017.07.005 | DOI Listing |
JAMA Netw Open
September 2025
Oncostat U1018, Institut National de la Santé et de la Recherche Médicale (INSERM), Ligue Contre le Cancer, Paris-Saclay University, Villejuif, France.
Importance: Antibiotics, steroids, and proton pump inhibitors (PPIs) are suspected to decrease the efficacy of immunotherapy.
Objective: To explore the association of comedications with overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC).
Design, Setting, And Participants: This nationwide retrospective cohort study used target trial emulations of patients newly diagnosed with NSCLC from January 2015 to December 2022, identified from the French national health care database.
Pharmacoeconomics
September 2025
Department of Pharmacy, Uppsala University, Box 580, 751 23, Uppsala, Sweden.
Background: Immune checkpoint inhibitors (ICIs) are clinically beneficial but associated with high costs that represent a growing challenge for healthcare budgets and may affect affordability, especially in resource-limited settings. Moreover, the healthcare sector is a significant source of greenhouse gas emissions, and medication-related waste-such as that from vial-based therapies-has been identified as a contributing factor. Alternative dosing strategies could reduce the environmental and financial impact of ICI therapy while maintaining clinical safety and efficacy.
View Article and Find Full Text PDFAppl Biochem Biotechnol
September 2025
Operating Room, Shanghai Tianyou Hospital, No.528, Zhennan Road, Putuo District, Shanghai, 200331, China.
Gastric cancer (GC) is a malignant tumor originating from the epithelial cells of the gastric mucosa. The 5-methylcytosine (mC) modification refers to the addition of a methyl group to the fifth carbon atom of cytosine in RNA molecules. This study aimed to investigate the role of NOL1/NOP2/SUN domain (NSUN)6 in GC and its underlying molecular mechanisms.
View Article and Find Full Text PDFMol Divers
September 2025
Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, 11942, Al Kharj, Saudi Arabia.
Cyclin-dependent kinase 20 (CDK20), also known as cell cycle-related kinase (CCRK), plays a pivotal role in hepatocellular carcinoma (HCC) progression by regulating β-catenin signaling and promoting uncontrolled proliferation. Despite its emerging significance, selective small-molecule inhibitors of CDK20 remain unexplored. In this study, a known CDK20 inhibitor, ISM042-2-048, was employed as a reference to retrieve structurally similar compounds from the PubChem database using an 85% similarity threshold.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
September 2025
Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, 560107, India.
This study aimed to synthesize and evaluate the anticancer activity of novel chalcone derivative against colon cancer by in vitro cytotoxicity against HCT-116 (Research Resource Identifiers:CVCL_D4JB) cell line and in vivo using EAC (Research Resource Identifiers: CVCL_1306) and DLA (Research Resource Identifiers: CVCL_VR37) cells inoculated Swiss albino mice. The present study aimed to synthesize the new chalcone derivatives and conduct its anti-colon cancer activity both in vitro and in vivo. The designed compounds were subjected to in silico studies like binding pocket analysis, molecular docking, and ADME studies.
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