title: Clonal evolution and tumor-initiating cells: New dimensions in cancer patient treatment.
abstract: Human cancer is not a uniform disease but a plethora of disparate tumor types and subtypes. The differences that exist between individual tumors (intertumoral heterogeneity) present a significant roadblock to the eradication of cancer. It has also become increasingly clear that variations across individual tumors (intratumoral heterogeneity) have important implications to cancer progression and treatment efficacy. Therefore, in order to improve patient care and develop novel chemotherapeutics, the evolving tumor landscape needs to be further explored. Next-generation sequencing (NGS) technologies are revolutionizing the cancer research arena by providing state-of-the-art, high-speed methods of genome sequencing at single-nucleotide resolution, thus enabling an unprecedented detection of tumor-specific genetic abnormalities. These anomalies can be quantified to reveal specific frequencies of DNA alterations that correspond to distinct clonal populations within a given tumor. As such, NGS approaches have also been utilized to explore the heterogeneous landscape of patient tumors as well as to match metastatic and/or recurrent growths and patient-derived engrafts. By sequencing in this manner--through time so to speak--cancer researchers can track shifting clonal populations, make important inferences about tumor evolution and potentially identify tumor subclones that could be viably targeted. This exciting new territory has important implications for the competing clonal evolution and cancer stem cell models of tumor heterogeneity, and also offers a new dimension for cancer treatment and profound hope for patients in the coming years.
authors.affiliation: a Princess Margaret Cancer Centre, University Health Network , Toronto , Ontario , Canada and.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Apostoli
authors.affiliation: a Princess Margaret Cancer Centre, University Health Network , Toronto , Ontario , Canada and.|b Department of Medical Biophysics , University of Toronto , Toronto , Ontario , Canada.
authors.forename: Laurie
authors.initials: L
authors.lastname: Ailles
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D060965:Clonal Evolution; D004252:DNA Mutational Analysis / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor
keywords: Cancer stem cells; clonal heterogeneity; next-generation sequencing; patient-derived xenografts; tumor-initiating cells