Genomic signatures to guide the use of chemotherapeutics.
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.
Potti
Anil
A
Duke Institute for Genome Sciences and Policy, Duke University, Box 3382, Durham, North Carolina 27710, USA.
Dressman
Holly K
HK
Bild
Andrea
A
Riedel
Richard F
RF
Chan
Gina
G
Sayer
Robyn
R
Cragun
Janiel
J
Cottrill
Hope
H
Kelley
Michael J
MJ
Petersen
Rebecca
R
Harpole
David
D
Marks
Jeffrey
J
Berchuck
Andrew
A
Ginsburg
Geoffrey S
GS
Febbo
Phillip
P
Lancaster
Johnathan
J
Nevins
Joseph R
JR
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*
D043823:Taxoids; D000077143:Docetaxel