A New Take on Preclinical Drug Trials for Glioblastoma Treatment

• Published in: Oncology fellows Vol. 14; no. 4
• Main Author: Lo Cascio, Costanza
• Format: Journal Article
• Language: English
• 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
• ISSN: 2767-3960

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.