Oxaliplatin and [Pt(R,R-DACH)(panobinostat-2H)] show nanomolar cytotoxicity towards diffuse intrinsic pontine glioma (DIPG)

Boulet, Marie H. C.; Marsh, Laura K.; Howarth, Alison; Woolman, A. M.; Farrer, Nicola J.

doi:10.1039/c9dt04862f

Cited by 8 publications

(2 citation statements)

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“…A paediatric glioma cell line was specifically chosen for investigation, due to our interest in developing novel anti-cancer compounds for these malignancies. 54 Complex 1·Gd was well-tolerated by KNS42 (paediatric glioblastoma) cells (viability <90%) across all concentrations and time-points tested. This indicated minimal cytotoxicity for 1·Gd , with IC 50 values exceeding 1000 μM ( Table 2 , Table S5, Fig.…”

Section: Resultsmentioning

confidence: 99%

Cell-permeable lanthanide–platinum(iv) anti-cancer prodrugs

et al. 2021

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Section: Resultsmentioning

confidence: 99%

Cell-permeable lanthanide–platinum(iv) anti-cancer prodrugs

et al. 2021

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“…Moreover, the sensitive location of these tumors and lack in surgical specimens (or even lack in the patient-derived cell lines) have hindered our understanding of the DIPG development, pathogenesis as well as discovery of effective targeted therapy. We and others recently have reported some new therapeutic targets and agents against DIPG, including natural products (e.g., Brefeldin A, Combretastatin A4); Emtansine conjugated to peptide nanofiber precursor (DM1-NFP); synthesized novel platinum (ii) complexes; combined AXL and HDAC inhibition [7][8][9][10][11][12]. However, most of these new treatments are still at preclinical stage, which require clinical trials to assess their efficacy and tolerability.…”

Section: Introductionmentioning

confidence: 99%

Targeting Sphingosine Kinase by ABC294640 against Diffuse Intrinsic Pontine Glioma (DIPG)

Dai¹,

Chen²,

Lin³

et al. 2020

J. Cancer

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As a highly aggressive pediatric brainstem tumor, diffuse intrinsic pontine glioma (DIPG) accounts for 10% to 20% of childhood brain tumors. The survival rate for DIPG remains very low, with a median survival time as less than one year even under radiotherapy, the current standard treatment. Moreover, over than 250 clinical trials have failed when trying to improve the survival compared to radiotherapy. The sphingolipid metabolism and related signaling pathways have been found closely related to cancer cell survival; however, the sphingolipid metabolism targeted therapies have never been investigated in DIPG. In the current study, the anti-DIPG activity of ABC294640, the only first-in-class orally available Sphingosine kinase (SphK) inhibitor was explored. Treatment with ABC294640 significantly repressed DIPG cell growth by inducing intracellular pro-apoptotic ceramides production and cell apoptosis. We also profiled ABC294640-induced changes in gene expression within DIPG cells and identified many new genes tightly controlled by sphingolipid metabolism, such as IFITM1 and KAL1. These genes are required for DIPG cell survival and display clinical relevance in DIPG patients' samples. Together, our findings in this study indicate that targeting sphingolipid metabolism may represent a promising strategy to improve DIPG treatment.

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