- Introduction to Cancer Systems Biology 5
- Systems biology in cancer research
Cancer is a complex disease. The cancer systems biology approach is very
effective in identifying drug targets, developing novel therapeutics and new
indications for existing drugs.7–10In addition to target and drug discovery,
cancer systems biology represents a valuable contribution to efforts toward
understanding the molecular mechanism of drugs in various cancer types5,
and regulation in cancer progression.^4
3.1. Target and drug discovery
Omics data in systems biology encompasses genome, transcriptome, pro-
teome, and metabolome. Reports using omics data in identifying therapeutic
targets and drugs have exponentially increased in the past decade. Here we
will introduce research work on target and drug discovery using genomics,
transcriptomics and proteomics approaches as well as bioinformatics and
network biology.
We can identify potential targets and biomarkers by mining TCGA
data — in particular, genomics and transcriptomics data. The targets and
biomarkers can be protein-coding mRNA and non-coding RNA such as
long non-coding RNAs (lncRNA) and microRNAs. In our recent work, we
identified 6 lncRNAs by analyzing the expression profiles of lncRNAs and
protein-coding genes between MYCN amplified and MYCN non-amplified
neuroblastoma (NB) patient samples from microarray and RNAseq datasets
and performing network analysis.^10 In the study, we found SNHG1 could be
a potential prognostic biomarker for high-risk NB intervention. Additionally,
we identified several microRNAs, such as miR-124-3p and miR-93-5p,
and RNA binding proteins: Synaptotagmin binding, cytoplasmic RNA-
interacting protein (SYNCRIP) and insulin-like growth factor-2 mRNA-
binding protein 3 (IGF2BP3), which could be potential therapeutic targets
for NB.^4
Besides genomics and transcriptomics, proteomics can also be used to
discover potential targets and biomarkers.^12 In our previous studies, we
utilized two dimensional (2D)-based proteomics coupling MS to identify
therapeutic targets or biomarkers for breast cancer,^9 lung cancer,^13 and
gastric cancer.14,15Using docking simulation for novel targets is helpful in
revealing their inhibitors. In our previous study, ATP synthase is a potential
drug target for breast and lung cancers. We further preformed homology
modeling and docking simulation and found aurovertin B and citreoviridin
to be potential drugs for breast and lung cancer.8,13In the final two chapters