ArticleJournal of experimental & clinical cancer research : CR2023
MYC drives platinum resistant SCLC that is overcome by the dual PI3K-HDAC inhibitor fimepinostat.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.Annals of medicine · 2026Review
- What are the Unmet Needs in Managing Digestive Neuroendocrine Carcinomas?Current oncology reports · 2026Review
- FOXA1 drives chemoresistance through activating Wnt pathway in small cell lung cancer.Translational lung cancer research · 2026Article
- From biology to the clinic: research evidence and therapeutic advances of TROP2-targeted antibody-drug conjugates in small cell lung cancer.Translational lung cancer research · 2026Review
- Targeting NHEJ activates STING signaling through MYC degradation to boost antitumor immunity in SCLC.Nature communications · 2026Article
- Epigenetic remodeling and apoptotic activation by Chidamide suppress small cell lung cancer in molecularly distinct subtypes.Discover oncology · 2026Article
- Targeting the BCKDK/BCLAF1/MYC/HK2 axis to alter aerobic glycolysis and overcome Trametinib resistance in lung cancer.Cell death and differentiation · 2025Article
- Article
- Genomic heterogeneity and clinical implications in gastrointestinal neuroendocrine carcinoma:ESMO gastrointestinal oncology · 2025Article
- TRIM21-mediated ubiquitination and phosphorylation of ERK1/2 promotes cell proliferation and drug resistance in pituitary adenomas.Neuro-oncology · 2025Article
- Article
- Overexpressed NEK2 contributes to progression and cisplatin resistance through activating the Wnt/β-catenin signaling pathway in cervical cancer.Cancer cell international · 2025Article
- Advancement Opportunities and Endeavor of Innovative Targeted Therapies for Small Cell Lung Cancer.International journal of biological sciences · 2025Review
- Review
- CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation.Signal transduction and targeted therapy · 2024Article
- C-Myc protein expression indicates unfavorable clinical outcome in surgically resected small cell lung cancer.World journal of surgical oncology · 2024Article
- Diapause-like Drug-Tolerant Persister State: The Key to Nirvana Rebirth.Medicina (Kaunas, Lithuania) · 2024Review
- Bromodomain Protein-directed Agents and MYC in Small Cell Lung Cancer.Current cancer drug targets · 2024Review
- Integrative analysis of blood transcriptome profiles in small-cell lung cancer patients for identification of novel chemotherapy resistance-related biomarkers.Frontiers in immunology · 2024Article
- Mechanisms of immunotherapy resistance in small cell lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2024Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSmall cell lung cancer (SCLC) is an aggressive neuroendocrine cancer with an appalling overall survival of less than 5% (Zimmerman et al. J Thor Oncol 14:768-83, 2019). Patients typically respond to front line platinum-based doublet chemotherapy, but almost universally relapse with drug resistant disease. Elevated MYC expression is common in SCLC and has been associated with platinum resistance. This study evaluates the capacity of MYC to drive platinum resistance and through screening identifies a drug capable of reducing MYC expression and overcoming resistance.
methodsElevated MYC expression following the acquisition of platinum resistance in vitro and in vivo was assessed. Moreover, the capacity of enforced MYC expression to drive platinum resistance was defined in SCLC cell lines and in a genetically engineered mouse model that expresses MYC specifically in lung tumors. High throughput drug screening was used to identify drugs able to kill MYC-expressing, platinum resistant cell lines. The capacity of this drug to treat SCLC was defined in vivo in both transplant models using cell lines and patient derived xenografts and in combination with platinum and etoposide chemotherapy in an autochthonous mouse model of platinum resistant SCLC.
resultsMYC expression is elevated following the acquisition of platinum resistance and constitutively high MYC expression drives platinum resistance in vitro and in vivo. We show that fimepinostat decreases MYC expression and that it is an effective single agent treatment for SCLC in vitro and in vivo. Indeed, fimepinostat is as effective as platinum-etoposide treatment in vivo. Importantly, when combined with platinum and etoposide, fimepinostat achieves a significant increase in survival.
conclusionsMYC is a potent driver of platinum resistance in SCLC that is effectively treated with fimepinostat.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.