ArticleCancer discovery2024
Acquired Cross-Resistance in Small Cell Lung Cancer due to Extrachromosomal DNA Amplification of MYC Paralogs.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
57 citing papers in PubMed, 54 citations in OpenAlex.
- Extrachromosomal DNA as a platform for epigenetic reprogramming in cancer.Molecular cancer · 2026Review
- Integrating molecular subtypes, genomics and functional dependencies to identify context-specific therapeutic vulnerabilities in small cell lung cancer.Biomarker research · 2026Review
- Multi-omics profiling of recurrence-associated extrachromosomal circular DNA characteristics and its prognostic potential in lung adenocarcinoma.Precision clinical medicine · 2026Article
- Extrachromosomal DNA in urothelial carcinoma: mechanisms and clinical applications.Nature reviews. Urology · 2026Review
- SCLC humanized mice identify T cell infiltration phenotypes in response to combination immune-radiation therapies.iScience · 2026Article
- FOXA1 drives chemoresistance through activating Wnt pathway in small cell lung cancer.Translational lung cancer research · 2026Article
- Loss of the USP22 deubiquitylase confers resistance to chemotherapy in small cell lung cancer.Nature communications · 2026Article
- KDM4B/DHX9 promotes chemoresistance in small-cell lung cancer through the MYCN-driven signaling pathway.Oncogene · 2026Article
- Cis and trans regulatory mechanisms of extrachromosomal DNA segregation.Nature cell biology · 2026Article
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- Extrachromosomal DNA Amplification as a Prognostic Factor for Cancer.Journal of personalized medicine · 2026Review
- The Impact of Targeting TRAF2 and NCK-Interacting Protein Kinase on Antitumor Effect and Tumor Immune Environment in c-MYC-High SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Review
- Review
- Fast and accurate resolution of ecDNA sequence using Cycle-Extractor.bioRxiv : the preprint server for biology · 2026Article
- Integrative Transcriptomic and Machine Learning Analysis of ecDNA-Associated Features for Studying Chemotherapy Resistance in TNBC.bioRxiv : the preprint server for biology · 2026Article
- Small Cell Lung Cancer Classification: Unraveling Heterogeneity to Enable Personalized Treatments.Cancer research · 2026Review
- Novel therapeutic strategy targeting STMN1 using chlorambucil-conjugated pyrrole-imidazole polyamide in small cell lung cancer.International journal of cancer · 2026Article
- Harnessing PDX and PDX 2.0: the next-generation paradigm for precision oncology and translational breakthroughs.Molecular cancer · 2026Review
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Authors and funding
25 authors at 6 institutions in 1 country.
Funding
Abstract
Small cell lung cancer (SCLC) presents as a highly chemosensitive malignancy but acquires cross-resistance after relapse. This transformation is nearly inevitable in patients but has been difficult to capture in laboratory models. Here, we present a preclinical system that recapitulates acquired cross-resistance, developed from 51 patient-derived xenograft (PDX) models. Each model was tested in vivo against three clinical regimens: cisplatin plus etoposide, olaparib plus temozolomide, and topotecan. These drug-response profiles captured hallmark clinical features of SCLC, such as the emergence of treatment-refractory disease after early relapse. For one patient, serial PDX models revealed that cross-resistance was acquired through MYC amplification on extrachromosomal DNA (ecDNA). Genomic and transcriptional profiles of the full PDX panel revealed that MYC paralog amplifications on ecDNAs were recurrent in relapsed cross-resistant SCLC, and this was corroborated in tumor biopsies from relapsed patients. We conclude that ecDNAs with MYC paralogs are recurrent drivers of cross-resistance in SCLC. SIGNIFICANCE: SCLC is initially chemosensitive, but acquired cross-resistance renders this disease refractory to further treatment and ultimately fatal. The genomic drivers of this transformation are unknown. We use a population of PDX models to discover that amplifications of MYC paralogs on ecDNA are recurrent drivers of acquired cross-resistance in SCLC. This article is featured in Selected Articles from This Issue, p. 695.
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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.