Drug discovery is important in cancer therapy and precision medicines. Traditional approaches
of drug discovery are mainly based on in vivo animal experiments and in vitro drug screening,
but these methods are usually expensive and laborious. In the last decade, omics data explosion
provides an opportunity for computational prediction of anti-cancer drugs, improving the efficiency of
drug discovery. High-throughput transcriptome data were widely used in biomarkers’ identification
and drug prediction by integrating with drug-response data. Moreover, biological network theory and
methodology were also successfully applied to the anti-cancer drug discovery, such as studies based
on protein-protein interaction network, drug-target network and disease-gene network. In this review,
we summarized and discussed the bioinformatics approaches for predicting anti-cancer drugs and drug
combinations based on the multi-omic data, including transcriptomics, toxicogenomics, functional genomics
and biological network. We believe that the general overview of available databases and current
computational methods will be helpful for the development of novel cancer therapy strategies.
IDH wild-type glioblastoma (GBM) has a dismal prognosis. A better understanding of tumor evolution holds the key to developing more effective treatment. Here we study glioblastoma's natural evolutionary trajectory by using rare, multifocal samples. We sequenced 61,062 single cells from eight multifocal IDH wild-type primary GBMs and defined a natural evolution signature (NES) of the tumor. We show that the NES significantly associates with the activation of transcription factors that regulate brain development, including MYBL2 and FOSL2. Hypoxia is involved in inducing NES-transition potentially via activation of the HIF1A-FOSL2 axis. High NES tumor cells could recruit and polarize bone marrow-derived macrophages through activation of the FOSL2-ANXA1-FPR1/3 axis. These polarized macrophages can efficiently suppress T cell activity and accelerate NES-transition in tumor cells. Moreover, The polarized macrophages could upregulate CCL2 to induce tumor cell migration.
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