ArticleAmerican journal of cancer research2017
Targeting MYC sensitizes malignant mesothelioma cells to PAK blockage-induced cytotoxicity.
Article in American journal of cancer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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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
9 citing papers in PubMed, 15 citations in OpenAlex.
- Article
- Antagonist of Growth Hormone-Releasing Hormone Potentiates the Antitumor Effect of Pemetrexed and Cisplatin in Pleural Mesothelioma.International journal of molecular sciences · 2022Article
- Salidroside overcomes dexamethasone resistance in T-acute lymphoblastic leukemia cells.Experimental and therapeutic medicine · 2021Article
- NF-κB-dependent Mechanism of Action of c-Myc Inhibitor 10058-F4: Highlighting a Promising Effect of c-Myc Inhibition in Leukemia Cells, Irrespective of p53 Status.Iranian journal of pharmaceutical research : IJPR · 2020Article
- Targeting Rho GTPase Signaling Networks in Cancer.Frontiers in cell and developmental biology · 2020Review
- Calcitriol Inhibits Viability and Proliferation in Human Malignant Pleural Mesothelioma Cells.Frontiers in endocrinology · 2020Article
- Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of human malignant pleural mesothelioma.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- A Functional 5'-UTR Polymorphism of MYC Contributes to Nasopharyngeal Carcinoma Susceptibility and Chemoradiotherapy Induced Toxicities.Journal of Cancer · 2019Article
- Progress in the Management of Malignant Pleural Mesothelioma in 2017.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Clinical management of malignant mesothelioma (MM) is very challenging due to marked resistance of this tumor to chemotherapy. Various mechanisms lead to a less than ideal drug concentration inside of MM cells, diminishing cytotoxicity. Consequently, single cytotoxic drugs achieve very modest response rates in MM patients, and combination regimens using standard and novel therapies have achieved only limited improvement in overall survival. Here, we demonstrate that MYC has either proliferative or pro-survival effects in MM cells during normal or stressed conditions, respectively. A MYC inhibitor 10058-F4 reduced MM cell proliferation via down regulation of cyclin D. Under serum starvation conditions, MM cells became quiescent, and the addition of MYC inhibitors triggered apoptosis in the resting MM cells. We also found that high concentrations of the PAK inhibitor PF3758309 killed MM cells, but the drug had only cytostatic effects at lower concentrations. These quiescent cells underwent apoptosis upon pharmacological inhibition of MYC. A novel MYC inhibitor KJ-Pyr-9 and a newer PAK inhibitor, FRAX597, also demonstrated marked cytotoxic cooperativity. Collectively, these findings demonstrate that targeting of MYC can sensitize MM cells and provide rationale for inhibition of MYC and PAK as a novel combinatory regimen for the treatment of this otherwise therapy-resistant, clinically incurable malignancy.
Indexed as
Identifiers
28861328PMC5574944W2982487575What OpenQuestion holds
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.