title: Genomic signatures to guide the use of chemotherapeutics.
abstract: Using in vitro drug sensitivity data coupled with Affymetrix microarray data, we developed gene expression signatures that predict sensitivity to individual chemotherapeutic drugs. Each signature was validated with response data from an independent set of cell line studies. We further show that many of these signatures can accurately predict clinical response in individuals treated with these drugs. Notably, signatures developed to predict response to individual agents, when combined, could also predict response to multidrug regimens. Finally, we integrated the chemotherapy response signatures with signatures of oncogenic pathway deregulation to identify new therapeutic strategies that make use of all available drugs. The development of gene expression profiles that can predict response to commonly used cytotoxic agents provides opportunities to better use these drugs, including using them in combination with existing targeted therapies.
authors.affiliation: Duke Institute for Genome Sciences and Policy, Duke University, Box 3382, Durham, North Carolina 27710, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Potti
authors.forename: Holly K
authors.initials: HK
authors.lastname: Dressman
authors.forename: Andrea
authors.initials: A
authors.lastname: Bild
authors.forename: Richard F
authors.initials: RF
authors.lastname: Riedel
authors.forename: Gina
authors.initials: G
authors.lastname: Chan
authors.forename: Robyn
authors.initials: R
authors.lastname: Sayer
authors.forename: Janiel
authors.initials: J
authors.lastname: Cragun
authors.forename: Hope
authors.initials: H
authors.lastname: Cottrill
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kelley
authors.forename: Rebecca
authors.initials: R
authors.lastname: Petersen
authors.forename: David
authors.initials: D
authors.lastname: Harpole
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Marks
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Ginsburg
authors.forename: Phillip
authors.initials: P
authors.lastname: Febbo
authors.forename: Johnathan
authors.initials: J
authors.lastname: Lancaster
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Nevins
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D015870:Gene Expression; D015894:Genome, Human; D006801:Humans; D010597:Pharmacogenetics; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D043823:Taxoids; D000077143:Docetaxel