A New Take on Preclinical Drug Trials for Glioblastoma Treatment

Intriguingly, when we examined the molecular consequences of quisinostat treatment in more detail, we found that short-term incubation with the drug resulted in extensive accumulation of DNA damage in GBM cells. The longer the incubation period with quisinostat, the greater the amount of DNA damage...

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Bibliographic Details
Published inOncology fellows Vol. 14; no. 4
Main Author Lo Cascio, Costanza
Format Journal Article
LanguageEnglish
Published Cranbury Intellisphere, LLC 14.12.2022
MultiMedia Healthcare Inc
Subjects
Blood-brain barrier
Brain cancer
Brain tumors
Cancer therapies
Cell cycle
Cell division
Clinical trials
DNA damage
DNA repair
Drug approval
Drugs
Glioblastoma multiforme
Medical prognosis
Prognosis
Radiation
Radiation therapy
Tumors
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Summary:Intriguingly, when we examined the molecular consequences of quisinostat treatment in more detail, we found that short-term incubation with the drug resulted in extensive accumulation of DNA damage in GBM cells. The longer the incubation period with quisinostat, the greater the amount of DNA damage to cancer cells. Because quisinostat acts as a DNA-damaging agent, we next questioned whether it could enhance the effects of radiation, which is the mainstay of GBM treatment.3 In other solid tumors, there is evidence that HDAC inhibitors can radio-sensitize cancer cells.8-12 We hypothesized that the accumulation of DNA damage induced by quisinostat in combination with radiation treatment would synergisti-cally reduce GBM cell viability. Interestingly, RNA-sequencing analysis of the resulting tumors revealed that combination therapy caused tumor cells to adopt neuronal-like cell fates, increase the levels of oxidative stress, and dampen the expression of genes involved in DNA repair and cell division. Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining.
ISSN:2767-3960
2767-3979