The molecular basis of the anticancer effect of statins

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Авг. 31, 2024

Abstract Statins, widely used cardiovascular drugs that lower cholesterol by inhibiting HMG-CoA reductase, have been increasingly recognized for their potential anticancer properties. This study elucidates the underlying mechanism, revealing statins exploit Synthetic Lethality, a principle where co-occurrence of two non-lethal events leads to cell death. Our computational analysis approximately 37,000 SL pairs identified as targeting genes involved in with metastatic genes. In vitro validation on various cancer lines confirmed efficacy statins. data-driven drug repurposing strategy provides molecular basis effects statins, offering translational opportunities oncology.

Язык: Английский

Computational Advancements in Drug Repurposing for Cancer Combination Therapy Prediction

Опубликована: Май 23, 2023

As cancer remains resistant to several modes of treatment, novel therapeutics are still under active investigation overcome treatment inefficacy in cancer. Given the high attrition rate de novo drug discovery, screening, and repurposing have offered time- cost-effective alternative strategies for identification potentially effective therapeutics. In contrast large-scale screens, computational approaches leverage increasing amounts biomedical data predict candidate therapeutic agents prior testing biological models. Current studies therapy prediction increasingly focused on combination therapies, as therapies numerous advantages over monotherapies. These include increased effect from synergistic interactions, reduced toxicity lowered doses, a risk resistance due multiple non-overlapping mechanisms action. This review provides summary classes methods used research, including networks, regression-based machine learning, classifier learning models, deep approaches, with goal presenting current progress field, particularly non-computational biologists. We conclude by discussing need further advancements technologies that incorporate disease mechanisms, characteristics, multi-omics data, clinical considerations generate patient-specific combinations, holistic integration will inevitably result optimal targeted

Язык: Английский

The molecular basis of the anticancer effect of statins

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 8, 2024

Abstract Statins, one of the most used class cardiovascular drugs with primary function reducing blood cholesterol levels, exert their effect by inhibiting enzyme HMG-CoA reductase, key player in biosynthesis. While indication for statins is prevention diseases, there has been growing interest potential anticancer effects. However, current evidence on these effects largely based epidemiological observations and preclinical research, not yet substantiated knowledge mechanisms behind it. Here we show that have an as they exploit principle Synthetic Lethality, a concept which combination two non-lethal genetic or molecular events results cell death impairment. When either occurs alone, it lethal, but when happen coupled, create lethal condition cell. In this work report emerged from computational data analysis performed approximately 37,000 synthetic lethality couples. We to select repurposable could target genes involved Lethality couples metastatic genes. validated our discovery vitro drug tests lines derived cancers breast, ovary, cervix. Our data-driven repurposing strategy allowed us understand basis statins, can be directly translated into practical clinical applications oncology.

Язык: Английский