ArticleCPT: pharmacometrics & systems pharmacology2023
Cell state-directed therapy - epigenetic modulation of gene transcription demonstrated with a quantitative systems pharmacology model of temozolomide.
Article in CPT: pharmacometrics & systems pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- IDENTIFICATION OF DISEASE-SPECIFIC VULNERABILITY STATES AT THE SINGLE-CELL LEVEL.bioRxiv : the preprint server for biology · 2025Article
- Network analyses of brain tumor multiomic data reveal pharmacological opportunities to alter cell state transitions.NPJ systems biology and applications · 2025Article
- A comprehensive review of computational cell cycle models in guiding cancer treatment strategies.NPJ systems biology and applications · 2024Review
- Network Analyses of Brain Tumor Patients' Multiomic Data Reveals Pharmacological Opportunities to Alter Cell State Transitions.Research square · 2024Article
- Network Analyses of Brain Tumor Patients' Multiomic Data Reveals Pharmacological Opportunities to Alter Cell State Transitions.bioRxiv : the preprint server for biology · 2024Article
- Cell state-directed therapy - epigenetic modulation of gene transcription demonstrated with a quantitative systems pharmacology model of temozolomide.CPT: pharmacometrics & systems pharmacology · 2023Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer therapy continues to be plagued by modest therapeutic advances. This is particularly evident in glioblastoma multiforme (GBM) wherein treatment failures are attributed to intratumoral heterogeneity (ITH), a dynamic process of cell state transitions or plasticity. To address ITH, we introduce the concept of cell state-directed (CSD) therapy through a quantitative systems pharmacology model of temozolomide (TMZ), a cornerstone of GBM drug therapy. The model consisting of multiple modules incorporated an epigenetic-based gene transcription-translation module that enabled CSD therapy. Numerous model simulations were conducted to demonstrate the potential impact of CSD therapy on TMZ activity. The simulations included those based on global sensitivity analyses to identify fragile nodes - MDM2 and XIAP - in the network, and also how an epigenetic modifier (birabresib) could overcome a mechanism of TMZ resistance. The positive results of CSD therapy on TMZ activity supports continued efforts to develop CSD therapy as a new anticancer approach.
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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.