ArticleMolecular oncology2017
Drug sensitivity and resistance testing identifies PLK1 inhibitors and gemcitabine as potent drugs for malignant peripheral nerve sheath tumors.
Article in Molecular oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06114004 (Phase I/II Randomized Clinical Trial of Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcomas), which is not on this map. Cited by 14 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.
Phase I/II Randomized Clinical Trial of Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcomas
Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Neurofibromatosis Type 1 and the Search for Effective Tumor Therapies Using High-Throughput Drug Screening.Current oncology (Toronto, Ont.) · 2025Review
- The first-in-Africa ex vivo drug sensitivity testing platform identifies novel drug combinations for South African leukaemia patient cohort.Scientific reports · 2025Article
- HN1L/AP-2γ/PLK1 signaling drives tumor progression and chemotherapy resistance in esophageal squamous cell carcinoma.Cell death & disease · 2022Article
- Review
- High-throughput ex vivo drug testing identifies potential drugs and drug combinations for NRAS-positive malignant melanoma.Translational oncology · 2022Article
- Combined Inhibition of SHP2 and MEK Is Effective in Models of NF1-Deficient Malignant Peripheral Nerve Sheath Tumors.Cancer research · 2020Article
- Systemic Treatment for Advanced and Metastatic Malignant Peripheral Nerve Sheath Tumors-A Sarcoma Reference Center Experience.Journal of clinical medicine · 2020Article
- Review
- Review
- Comprehensive analysis reveals a metabolic ten-gene signature in hepatocellular carcinoma.PeerJ · 2020Article
- Polo-like kinase 1 as a therapeutic target for malignant peripheral nerve sheath tumors (MPNST) and schwannomas.American journal of cancer research · 2020Article
- A PLK1 kinase inhibitor enhances the chemosensitivity of cisplatin by inducing pyroptosis in oesophageal squamous cell carcinoma.EBioMedicine · 2019Article
- Inferior survival for patients with malignant peripheral nerve sheath tumors defined by aberrant TP53.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2018Article
- Neurofibromin level directs RAS pathway signaling and mediates sensitivity to targeted agents in malignant peripheral nerve sheath tumors.Oncotarget · 2018Article
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 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with malignant peripheral nerve sheath tumor (MPNST), a rare soft tissue cancer associated with loss of the tumor suppressor neurofibromin (NF1), have poor prognosis and typically respond poorly to adjuvant therapy. We evaluated the effect of 299 clinical and investigational compounds on seven MPNST cell lines, two primary cultures of human Schwann cells, and five normal bone marrow aspirates, to identify potent drugs for MPNST treatment with few side effects. Top hits included Polo-like kinase 1 (PLK1) inhibitors (volasertib and BI2536) and the fluoronucleoside gemcitabine, which were validated in orthogonal assays measuring viability, cytotoxicity, and apoptosis. DNA copy number, gene expression, and protein expression were determined for the cell lines to assess pharmacogenomic relationships. MPNST cells were more sensitive to BI2536 and gemcitabine compared to a reference set of 94 cancer cell lines. PLK1, RRM1, and RRM2 mRNA levels were increased in MPNST compared to benign neurofibroma tissue, and the protein level of PLK1 was increased in the MPNST cell lines compared to normal Schwann cells, indicating an increased dependence on these drug targets in malignant cells. Furthermore, we observed an association between increased mRNA expression of PLK1, RRM1, and RRM2 in patient samples and worse disease outcome, suggesting a selective benefit from inhibition of these genes in the most aggressive tumors.
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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 Socratic graph.