ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Single-Cell Profiling Reveals Metabolic Reprogramming as a Resistance Mechanism in
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Cell-free DNA for the detection of emerging treatment failure in relapsed/ refractory multiple myeloma.Leukemia · 2022Trial
- Identification of Metabolic Biomarkers in Bone Marrow Aspirate for Diagnosis, Prognosis, and Therapeutic Monitoring in Pediatric Langerhans Cell Histiocytosis.Annals of laboratory medicine · 2026Article
- Decoding immunotherapy resistance in multiple myeloma: genetic insights and approaches to counter resistance.Science China. Life sciences · 2026Review
- Promoter hypermethylation as a reversible mechanism of resistance to GPRC5D-directed therapy in multiple myeloma.Haematologica · 2026Article
- The controversial role of metabolic reprogramming in anti-tumor therapy resistance.Discover oncology · 2026Review
- Darunavir analog precursors target mitochondrial metabolism in multiple myeloma and CLL.Cancer cell international · 2025Article
- Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies.Cell death discovery · 2025Review
- Single-cell sequencing reveals the mechanisms of multiple myeloma progression: clarity or confusion?Annals of hematology · 2025Review
- Loss of Heterozygosity and Mutations in the RAS-ERK Pathway Genes in Tumor Cells of Various Loci in Multiple Myeloma.International journal of molecular sciences · 2024Article
- BRAF - a tumour-agnostic drug target with lineage-specific dependencies.Nature reviews. Clinical oncology · 2024Review
- Novel Insights into the Initiation, Evolution, and Progression of Multiple Myeloma by Multi-Omics Investigation.Cancers · 2024Review
- Resolving therapy resistance mechanisms in multiple myeloma by multiomics subclone analysis.Blood · 2023Article
- Essential procedures of single-cell RNA sequencing in multiple myeloma and its translational value.Blood science (Baltimore, Md.) · 2023Review
- Review
- [Latest Findings on the Mechanism of the Interaction Between Multiple Myeloma Cells and Bone Marrow Microenvironment].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023Review
- Article
- ABC portal: a single-cell database and web server for blood cells.Nucleic acids research · 2023Article
- Integrative Analysis of Bulk RNA-Seq and Single-Cell RNA-Seq Unveils Novel Prognostic Biomarkers in Multiple Myeloma.Biomolecules · 2022Article
- Current perspectives on interethnic variability in multiple myeloma: Single cell technology, population pharmacogenetics and molecular signal transduction.Translational oncology · 2022Article
- Malignant clonal evolution drives multiple myeloma cellular ecological diversity and microenvironment reprogramming.Molecular cancer · 2022Article
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 1 country.
Funding
Abstract
purposeAlthough remarkably effective in some patients, precision medicine typically induces only transient responses despite initial absence of resistance-conferring mutations. Using EXPERIMENTAL
designFull-length single-cell RNA (scRNA) sequencing (scRNA-seq) was conducted on 3 patients with
resultsProfiling by scRNA-seq revealed rapid cellular state changes in response to BRAF/MEK inhibition in patients with myeloma and cell lines. Transcriptional adaptation preceded detectable outgrowth of genetically discernible drug-resistant clones and was associated with widespread enhancer remodeling. As a dominant vulnerability, dependency on oxidative phosphorylation (OxPhos) was induced. In treated individuals, OxPhos was activated at the time of relapse and showed inverse correlation to MAPK activation. Metabolic flux analysis confirmed OxPhos as a preferential energetic resource of drug-persistent myeloma cells.
conclusionsThis study demonstrates that cancer cells have the ability to rapidly adapt to precision treatments through transcriptional state changes, epigenetic adaptation, and metabolic rewiring, thus facilitating the development of refractory disease while simultaneously exposing novel vulnerabilities.
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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.