title: Cancer systems biology in the genome sequencing era: part 2, evolutionary dynamics of tumor clonal networks and drug resistance.
abstract: A tumor often consists of multiple cell subpopulations (clones). Current chemo-treatments often target one clone of a tumor. Although the drug kills that clone, other clones overtake it and the tumor recurs. Genome sequencing and computational analysis allows to computational dissection of clones from tumors, while singe-cell genome sequencing including RNA-Seq allows profiling of these clones. This opens a new window for treating a tumor as a system in which clones are evolving. Future cancer systems biology studies should consider a tumor as an evolving system with multiple clones. Therefore, topics discussed in Part 2 of this review include evolutionary dynamics of clonal networks, early-warning signals (e.g., genome duplication events) for formation of fast-growing clones, dissecting tumor heterogeneity, and modeling of clone-clone-stroma interactions for drug resistance. The ultimate goal of the future systems biology analysis is to obtain a 'whole-system' understanding of a tumor and therefore provides a more efficient and personalized management strategies for cancer patients.
authors.affiliation: National Research Council Canada, Montreal, Canada. edwin.wang@cnrc-nrc.gc.ca
authors.forename: Edwin
authors.initials: E
authors.lastname: Wang
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zou
authors.forename: Naif
authors.initials: N
authors.lastname: Zaman
authors.forename: Lenore K
authors.initials: LK
authors.lastname: Beitel
authors.forename: Mark
authors.initials: M
authors.lastname: Trifiro
authors.forename: Miltiadis
authors.initials: M
authors.lastname: Paliouras
mesh_terms: D019070:Cell Lineage / Q000235:genetics; D053263:Gene Regulatory Networks; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA / Q000379:methods*; D059010:Single-Cell Analysis / Q000379:methods; D049490:Systems Biology / Q000379:methods*; D059016:Tumor Microenvironment / Q000235:genetics
keywords: Cancer evolution; Drug resistance; Early-warning signal; Genome sequencing; Personalized medicine; Signaling network; Systems biology; Tumor clone; Tumor heterogeneity