RNA data development of cancer cell lines and patients

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

The general motivation for this project is as stated for ZIC BC 011820, DNA Data Development project. That is, we contend that cancer arises in a multi-factorial manner, employing a combination of genetic, transcript of epigenetic alterations to become increasingly undifferentiated, proliferative, invasive and metastatic. As for the DNA, both individual genes and molecular networks advantageous to these changes are altered at the transcript level in this process. Our goal is to gain understanding of both the disease progression and the choice of more targeted and efficacious cancer treatments. For the current anti-cancer drugs, there is of course knowledge regarding their mechanism of action and biological effects. However, even with this information both FDA-approved and clinical-trial drugs, often have generally poorly understood off-target effects as well as variable efficacy when used. We seek to improve understanding of the use of compound activity and genomic profiling data over well-characterized cell line panels to attempt computational prediction of molecular drug response determinants. Our CellMiner suite of web-applications provide the functionality to make comparisons between RNA parameters and drug activities as well as other molecular and phenotypic data. For the bioinformaticians, we allow database downloads. In the last year, we have added i) RNA sequencing for the triple negative breast cancer (TNBC) MDA-MB468 and BT549 parental and chronic exposure to acetalax cells lines as well as their GSEA comparison (PMID 39041239), ii) scatter plots of five TNBC cell lines TRPM4 expression verses acetalax activity as well as all available cancer cell lines TRPM4 expression verses acetalax activity (PMID 39041239), iii) comparisons between transcript expression patterns and acetalax and bisacodyl activity in TNBC cell lines using GSEA as well as scatter plots (PMID 39932272), iv) prediction of acetalax and bisacodyl activity in TNBC using transcript expression (PMID 39932272), v) transcriptome data for four sarcoma cell line sets including comparisons to promotor methylation and drug activities (PMID 38868205), vi) RNAseq analysis of PDX samples, vii) comparison of promoter to promoter plus body methylation to transcript expression in glioblastomas (PMID 40464417) and viii) transcript data for adrenocortical carcinoma patients from multiple sources (PMID 40291702).