title: A braided cancer river connects tumor heterogeneity and precision medicine.
abstract: With the ever-increasing complexity of tumor heterogeneity (TH) discovered through cancer genome sequencing, it is apparent that TH has become the biggest hurdle for precision cancer therapeutics. Through studying the genomics of exceptional responders to targeted therapeutic agents in kidney cancer, we demonstrated parallel convergent gene/pathway/capability/function evolution of kidney cancer in the context of TH, which prompted us to propose a new cancer evolution model "the braided cancer river model". Based on this model, we might be able to outsmart a given cancer type within an individual patient through simultaneously inhibiting preferred parallel pathways or sequential nodes. Thus, the goals of this perspective are to define tumor heterogeneity, discuss tumor evolution, introduce braided cancer river model, and improve precision medicine.
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. hsiehj@mskcc.org.
authors.forename: James J
authors.initials: JJ
authors.lastname: Hsieh
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.|Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors.forename: Emily H
authors.initials: EH
authors.lastname: Cheng
keywords: Braided cancer river model; Branched evolution; Kidney cancer; MTOR inhibitors; Parallel convergent gene/pathway/capability/function evolution; Precision medicine; Tumor heterogeneity; VEGF inhibitors