ArticleScience advances2019
SLC36A1-mTORC1 signaling drives acquired resistance to CDK4/6 inhibitors.
Article in Science advances, 2019. 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, 46 citations in OpenAlex.
- Targeting SUV39H2 exon skipping reverses resistance to CDK4/6 inhibitors via transcriptional activation of p21.Science advances · 2026Article
- Solute Carrier transporters in tumor metabolism and immune modulation: implications for therapy.Journal of translational medicine · 2026Review
- Metformin sensitizes non-small cell lung cancer to CDK4/6 inhibitor treatment by reducing lysosomal trapping.Science China. Life sciences · 2026Article
- Advances in Cutaneous Melanoma Therapy: The Emerging Role of CDK4/6 Inhibitors.Pharmacological research · 2025Review
- Review
- Inhibition of glutaminase elicits senolysis in therapy-induced senescent melanoma cells.Cell death & disease · 2024Article
- Discovery of a small molecule that inhibits Bcl-3-mediated cyclin D1 expression in melanoma cells.BMC cancer · 2024Article
- Inhibitors Targeting the F-BOX Proteins.Cell biochemistry and biophysics · 2023Review
- Sequential activation of E2F via Rb degradation and c-Myc drives resistance to CDK4/6 inhibitors in breast cancer.Cell reports · 2023Article
- miR-30e-5p-mediated FOXD1 promotes cell proliferation by blocking cellular senescence and apoptosis through p21/CDK2/Rb signaling in head and neck carcinoma.Cell death discovery · 2023Article
- Article
- Differences in metabolic transport and resistance mechanisms of Abemaciclib, Palbociclib, and Ribociclib.Frontiers in pharmacology · 2023Review
- Comprehensive analysis of an autophagy-related prognostic model for predicting survival based on TCGA and ICGC database in hepatocellular carcinoma patients.Journal of gastrointestinal oncology · 2022Article
- ESCCAL-1 promotes cell-cycle progression by interacting with and stabilizing galectin-1 in esophageal squamous cell carcinoma.NPJ precision oncology · 2022Article
- CDK4 and CDK6 kinases: From basic science to cancer therapy.Science (New York, N.Y.) · 2022Review
- CDK4/6 inhibitor resistance: A bibliometric analysis.Frontiers in oncology · 2022Article
- Transcriptome Analysis of Solute Carrier-Associated Genes in Hepatocellular Carcinoma: Friend or Foe?Frontiers in genetics · 2022Article
- Review
- Metabolic modulation by CDK4/6 inhibitor promotes chemokine-mediated recruitment of T cells into mammary tumors.Cell reports · 2021Article
- Key transporters leading to specific protoporphyrin IX accumulation in cancer cell following administration of aminolevulinic acid in photodynamic therapy/diagnosis.International journal of clinical oncology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The cyclin-dependent kinase 4/6 (CDK4/6) kinase is dysregulated in melanoma, highlighting it as a potential therapeutic target. CDK4/6 inhibitors are being evaluated in trials for melanoma and additional cancers. While beneficial, resistance to therapy is a concern, and the molecular mechanisms of such resistance remain undefined. We demonstrate that reactivation of mammalian target of rapamycin 1 (mTORC1) signaling through increased expression of the amino acid transporter, solute carrier family 36 member 1 (SLC36A1), drives resistance to CDK4/6 inhibitors. Increased expression of SLC36A1 reflects two distinct mechanisms: (i) Rb loss, which drives SLC36A1 via reduced suppression of E2f; (ii) fragile X mental retardation syndrome-associated protein 1 overexpression, which promotes SLC36A1 translation and subsequently mTORC1. Last, we demonstrate that a combination of a CDK4/6 inhibitor with an mTORC1 inhibitor has increased therapeutic efficacy in vivo, providing an important avenue for improved therapeutic intervention in aggressive melanoma.
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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.