Artificial intelligence to guide precision anticancer therapy with multitargeted kinase inhibitors

人工智能指导多靶点激酶抑制剂精准抗癌治疗

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作者:Manali Singha #, Limeng Pu #, Brent A Stanfield, Ifeanyi K Uche, Paul J F Rider, Konstantin G Kousoulas, J Ramanujam, Michal Brylinski

Background

Vast amounts of rapidly accumulating biological data related to cancer and a remarkable progress in the field of artificial intelligence (AI) have paved the way for precision oncology. Our recent contribution to this area of research is CancerOmicsNet, an AI-based system to predict the therapeutic effects of multitargeted kinase inhibitors across various cancers. This approach was previously demonstrated to outperform other deep learning

Conclusions

CancerOmicsNet is a promising AI-based platform to help guide the development of new approaches in precision oncology involving a variety of tumor types and therapeutics.

Methods

CancerOmicsNet integrates multiple heterogeneous data by utilizing a deep graph learning model with sophisticated attention propagation mechanisms to extract highly predictive features from cancer-specific networks. The AI-based system was devised to provide more accurate and robust predictions than data-driven therapeutic discovery using gene signature reversion.

Results

Selected CancerOmicsNet predictions obtained for "unseen" data are positively validated against the biomedical literature and by live-cell time course inhibition assays performed against breast, pancreatic, and prostate cancer cell lines. Encouragingly, six molecules exhibited dose-dependent antiproliferative activities, with pan-CDK inhibitor JNJ-7706621 and Src inhibitor PP1 being the most potent against the pancreatic cancer cell line Panc 04.03. Conclusions: CancerOmicsNet is a promising AI-based platform to help guide the development of new approaches in precision oncology involving a variety of tumor types and therapeutics.

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