ArticleMolecular systems biology2018
Targeting CDK2 overcomes melanoma resistance against BRAF and Hsp90 inhibitors.
Article in Molecular systems biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 66 citations in OpenAlex.
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- Targeting CDK2 and other novel cell cycle targets for breast cancer therapy.Expert opinion on therapeutic targets · 2025Review
- Protein Kinase CK2 Inhibition Represents a Pharmacological Chance for the Treatment of Skin Diseases.International journal of molecular sciences · 2025Review
- Spatiotemporal Profiling Defines Persistence and Resistance Dynamics during Targeted Treatment of Melanoma.Cancer research · 2025Article
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- Targeting CDK2 to combat drug resistance in cancer therapy.Future oncology (London, England) · 2024Review
- Protein translation: biological processes and therapeutic strategies for human diseases.Signal transduction and targeted therapy · 2024Review
- P129, a pyrazole ring-containing isolongifolanone-derivate: synthesis and investigation of anti-glioma action mechanism.Discover oncology · 2024Article
- New spiro-indeno[1,2-Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Significance of RB Loss in Unlocking Phenotypic Plasticity in Advanced Cancers.Molecular cancer research : MCR · 2023Article
- Reconstruction of the cell pseudo-space from single-cell RNA sequencing data with scSpace.Nature communications · 2023Article
- A transcriptional evaluation of the melanoma and squamous cell carcinoma TIL compartment reveals an unexpected spectrum of exhausted and functional T cells.Frontiers in oncology · 2023Article
- Investigation of evolutionary dynamics for drug resistance in 3D spheroid model system using cellular barcoding technology.PloS one · 2023Article
- Toward the analysis of functional proteoforms using mass spectrometry-based stability proteomics.Frontiers in analytical science · 2023Article
- Design, synthesis, biological evaluation and molecular docking study of 2,4-diarylimidazoles and 2,4-bis(benzyloxy)-5-arylpyrimidines as novel HSP90 N-terminal inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Concomitant Use of Sulforaphane Enhances Antitumor Efficacy of Sunitinib in Renal Cell Carcinoma In Vitro.Cancers · 2022Article
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- The heat shock response and small molecule regulators.European journal of medicinal chemistry · 2021Review
- Targeting cell-cycle machinery in cancer.Cancer cell · 2021Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Novel therapies are undergoing clinical trials, for example, the Hsp90 inhibitor, XL888, in combination with BRAF inhibitors for the treatment of therapy-resistant melanomas. Unfortunately, our data show that this combination elicits a heterogeneous response in a panel of melanoma cell lines including PDX-derived models. We sought to understand the mechanisms underlying the differential responses and suggest a patient stratification strategy. Thermal proteome profiling (TPP) identified the protein targets of XL888 in a pair of sensitive and unresponsive cell lines. Unbiased proteomics and phosphoproteomics analyses identified CDK2 as a driver of resistance to both BRAF and Hsp90 inhibitors and its expression is regulated by the transcription factor MITF upon XL888 treatment. The CDK2 inhibitor, dinaciclib, attenuated resistance to both classes of inhibitors and combinations thereof. Notably, we found that MITF expression correlates with CDK2 upregulation in patients; thus, dinaciclib would warrant consideration for treatment of patients unresponsive to BRAF-MEK and/or Hsp90 inhibitors and/or harboring MITF amplification/overexpression.
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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.