title: Database of genomic biomarkers for cancer drugs and clinical targetability in solid tumors.
abstract: Comprehensive genomic profiling is expected to revolutionize cancer therapy. In this Prospective, we present the prevalence of mutations and copy-number alterations with predictive associations across solid tumors at different levels of stringency for gene-drug targetability. More than 90% of The Cancer Genome Atlas samples have potentially targetable alterations, the majority with multiple events, illustrating the challenges for treatment prioritization given the complexity of the genomic landscape. Nearly 80% of the variants in rarely mutated oncogenes are of uncertain functional significance, reflecting the gap in our understanding of the relevance of many alterations potentially linked to therapeutic actions. Access to targeted agents in early clinical trials could affect treatment decision in 75% of patients with cancer. Prospective implementation of large-scale molecular profiling and standardized reports of predictive biomarkers are fundamental steps for making precision cancer medicine a reality.
authors: Sage Bionetworks, Fred Hutchinson Cancer Research Center, Seattle, Washington. rodrigo.dienstmann@sagebase.org.
authors: Rodrigo
authors: R
authors: Dienstmann
authors: Sage Bionetworks, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: In Sock
authors: IS
authors: Jang
authors: Sage Bionetworks, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Brian
authors: B
authors: Bot
authors: Sage Bionetworks, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Stephen
authors: S
authors: Friend
authors: Sage Bionetworks, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Justin
authors: J
authors: Guinney
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D030541:Databases, Genetic; D023281:Genomics / Q000379:methods*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
references: Science. 2013 Mar 29;339(6127):1546-58
references: 23539594
references: Oncotarget. 2013 Feb;4(2):310-5
references: 23470635
references: Cancer Res. 2013 Aug 15;73(16):5195-205
references: 23786770
references: Eur J Cancer. 2013 Jul;49(10):2345-55
references: 23578570
references: J Clin Oncol. 2013 May 20;31(15):1874-84
references: 23589551
references: Cancer Discov. 2013 Nov;3(11):1238-44
references: 23950206
references: Nature. 2014 Jan 23;505(7484):495-501
references: 24390350
references: Cancer Discov. 2014 May;4(5):546-53
references: 24625776
references: Nat Med. 2014 Jun;20(6):682-8
references: 24836576
references: Mol Oncol. 2014 Jul;8(5):859-73
references: 24768039
references: Nat Biotechnol. 2014 Jul;32(7):644-52
references: 24952901
references: Cancer Discov. 2014 Sep;4(9):1014-21
references: 24934408
references: Nat Commun. 2014;5:4846
references: 25204415
references: Genome Biol. 2014;15(8):438
references: 25222080
references: Clin Cancer Res. 2013 Jul 1;19(13):3693-702
references: 23658459
references: Science. 1997 Nov 7;278(5340):1064-8
references: 9353181
references: N Engl J Med. 2006 Jun 15;354(24):2619-21
references: 16775247
references: N Engl J Med. 2010 Oct 28;363(18):1693-703
references: 20979469
references: PLoS One. 2011;6(1):e15640
references: 21253578
references: J Clin Oncol. 2012 Mar 10;30(8):863-70
references: 22215748
references: N Engl J Med. 2012 May 24;366(21):2038-40
references: 22621641
references: Cancer Discov. 2011 Jun;1(1):78-89
references: 22328973
references: Science. 2012 Oct 12;338(6104):221
references: 22923433
references: Clin Cancer Res. 2013 Jan 15;19(2):480-90
references: 23186780
references: Cancer Cell. 2013 May 13;23(5):603-17
references: 23680147