Identification of dual-purpose therapeutic targets implicated in aging and glioblastoma multiforme using PandaOmics - an AI-enabled biological target discovery platform

Aging (Albany NY). 2023 Apr 26;15(8):2863-2876. doi: 10.18632/aging.204678. Epub 2023 Apr 26.

Abstract

Glioblastoma Multiforme (GBM) is the most aggressive and most common primary malignant brain tumor. The age of GBM patients is considered as one of the disease's negative prognostic factors and the mean age of diagnosis is 62 years. A promising approach to preventing both GBM and aging is to identify new potential therapeutic targets that are associated with both conditions as concurrent drivers. In this work, we present a multi-angled approach of identifying targets, which takes into account not only the disease-related genes but also the ones important in aging. For this purpose, we developed three strategies of target identification using the results of correlation analysis augmented with survival data, differences in expression levels and previously published information of aging-related genes. Several studies have recently validated the robustness and applicability of AI-driven computational methods for target identification in both cancer and aging-related diseases. Therefore, we leveraged the AI predictive power of the PandaOmics TargetID engine in order to rank the resulting target hypotheses and prioritize the most promising therapeutic gene targets. We propose cyclic nucleotide gated channel subunit alpha 3 (CNGA3), glutamate dehydrogenase 1 (GLUD1) and sirtuin 1 (SIRT1) as potential novel dual-purpose therapeutic targets to treat aging and GBM.

Keywords: GBM; PandaOmics; aging; glioblastoma; target discovery.

MeSH terms

  • Aging / genetics
  • Artificial Intelligence
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / metabolism
  • Glioblastoma* / drug therapy
  • Glioblastoma* / genetics
  • Glioblastoma* / metabolism
  • Humans