QSAR-Based Drug Repurposing and RNA-Seq Metabolic Networks Highlight Treatment Opportunities for Hepatocellular Carcinoma Through Pyrimidine Starvation DOI Open Access

Nicholas Dale D. Talubo,

Estela Máris Amorim Cruz,

Peter Matthew Paul Fowler

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 903 - 903

Published: March 6, 2025

Background/Objectives: The molecular heterogeneity and metabolic flexibility of Hepatocellular Carcinoma (HCC) pose significant challenges to the efficacy systemic therapy for advanced cases. Early screening difficulties often delay diagnosis, leading more stages at presentation. Combined with inconsistent responses current therapies, HCC continues have one highest mortality rates among cancers. Thus, this paper seeks contribute development options through consideration HCC's vulnerabilities lay groundwork future in vitro studies. Methods: Transcriptomic data were used calculate single double knockout using genetic Minimal Cut Sets. Furthermore, QSAR modeling, drug repositioning opportunities assessed inhibit selected genes. Results: Two that also annotated as essential pairs found within pyrimidine metabolism pathway HCC, wherein either DHODH or TYMS is potentially disruptive proliferation. result flux balance analysis gene simulation indicated a decrease biomass production. Three machine learning algorithms their performance predicting pIC50 given compound SVM-rbf performed best on unseen achieving an R2 0.82 0.81 TYMS. For DHODH, drugs Oteseconazole, Tipranavir, Lusutrombopag identified potential inhibitors. TYMS, Tadalafil, Dabigatran, Baloxavir Marboxil, Candesartan Cilexetil showed promise Conclusions: Overall, study suggests testing assess capabilities inducing starvation HCC.

Language: Английский

QSAR-Based Drug Repurposing and RNA-Seq Metabolic Networks Highlight Treatment Opportunities for Hepatocellular Carcinoma Through Pyrimidine Starvation DOI Open Access

Nicholas Dale D. Talubo,

Estela Máris Amorim Cruz,

Peter Matthew Paul Fowler

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 903 - 903

Published: March 6, 2025

Background/Objectives: The molecular heterogeneity and metabolic flexibility of Hepatocellular Carcinoma (HCC) pose significant challenges to the efficacy systemic therapy for advanced cases. Early screening difficulties often delay diagnosis, leading more stages at presentation. Combined with inconsistent responses current therapies, HCC continues have one highest mortality rates among cancers. Thus, this paper seeks contribute development options through consideration HCC's vulnerabilities lay groundwork future in vitro studies. Methods: Transcriptomic data were used calculate single double knockout using genetic Minimal Cut Sets. Furthermore, QSAR modeling, drug repositioning opportunities assessed inhibit selected genes. Results: Two that also annotated as essential pairs found within pyrimidine metabolism pathway HCC, wherein either DHODH or TYMS is potentially disruptive proliferation. result flux balance analysis gene simulation indicated a decrease biomass production. Three machine learning algorithms their performance predicting pIC50 given compound SVM-rbf performed best on unseen achieving an R2 0.82 0.81 TYMS. For DHODH, drugs Oteseconazole, Tipranavir, Lusutrombopag identified potential inhibitors. TYMS, Tadalafil, Dabigatran, Baloxavir Marboxil, Candesartan Cilexetil showed promise Conclusions: Overall, study suggests testing assess capabilities inducing starvation HCC.

Language: Английский

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