Matches in SemOpenAlex for { <https://semopenalex.org/work/W2567253913> ?p ?o ?g. }
Showing items 1 to 100 of
100
with 100 items per page.
- W2567253913 abstract "Purpose: Despite major progress in the molecular characterization of ovarian cancers (OC), women with recurrent, advanced stage OC continue to be treated with cytotoxic chemotherapy agents that have poor overall response rates. This contrasts with the treatment paradigm for other cancers, where outcomes have been improved by selecting treatment based upon “actionable” genomic alteration(s) that are in drug-targetable pathways. There is a need to determine if molecular profiling for OC patients can improve treatment outcomes. Such a profile should comprehensively identify “actionable” genetic aberrations as well as measure expression levels of proteins that are drug targets/response biomarkers. Methods: The presence of mutations or alterations [e.g., copy number (CN)] in ~200 genes was determined using a validated exon-capture sequencing platform (Foundation Medicine, Inc) and protein levels of ERBB2, EGFR, ESR1, cMET, PTEN, RB1, and p16 were measured by IHC (Caris Life Sciences and Clarient, Inc). Formalin-fixed, paraffin-embedded tumor blocks were obtained following informed patient consent. Results were provided to the patient and medical team to enable informed decisions regarding subsequent treatment. The effectiveness of targeted therapies was assessed by CA125 levels and/or diagnostic imaging scans; clinical data were captured in an encrypted and privacy-protected database. Results: 88 tumor specimens (20 primary, 68 recurrent) were analyzed from 85 patients, most diagnosed with stage III/IV OC [60 high grade serous (HGS) or mixed histology, 3 LG serous, 4 SB, 4 MMMT, 5 CC, 4 E, 1 M, 4 NOS]. A median of 3 (range 0-6) “actionable” alterations were detected/tumor with TP53 the most frequently altered (77%, 90% in HGS). Genes in key targetable pathways were altered: PI3K-AKT-mTOR (34%), RAS-MAPK (35%), HR DNA repair (31%; 20%: BRCA1/2), cell cycle (36%), GF receptor TK (23%), and MYC (22%). CN changes for PIK3CA, AKT3, and KRAS were common in HGS, while mutations were common in non-HGS. PTEN, RB1, and p16 protein loss were primarily detected in non-HGS tumors. Most genetic alterations in CDKN2A, RB1, and PTEN correlated with protein levels. Profile-directed treatment options were pursued for at least ten patients, who received PARP inhibitor olaparib (somatic BRCA2 MUT), mTOR inhibitors everolimus (PIK3CA MUT; TSC1 DEL; NF1 MUT/PTEN loss) or temsirolimus (NF1 MUT), MEK inhibitor trametinib (KRAS MUT), MET/ALK inhibitor crizotinib (high cMET), combination PI3K GDC-0941 and MEK inhibitor GDC-0973 (PIK3CA MUT /KRAS MUT), hedgehog inhibitor vismodegib (PTCH1 MUT), FGFR inhibitor JNJ-42756493 (FGFR1 AMP) and elicited 3 partial responses and 2 extended remissions with 2 patients still on treatment. Conclusion: Comprehensive tumor molecular profiling approaches that measure protein, as well as DNA mutations and copy number alterations in targetable pathways are needed to identify drugs that are appropriate for each patient’s tumor profile. Early evidence suggests that advanced stage OC patients may benefit from targeted drugs and additional work is needed to understand if profile-directed treatment will provide benefit beyond currently available chemotherapy options. Citation Format: D. A. Zajchowski, PhD, M. Whitlow, PhD, K. M. Zajchowski, L. K. Shawver, PhD. Genomic profiles inform treatment decisions and enable future drug/biomarker discovery [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-TECH-1127." @default.
- W2567253913 created "2017-01-06" @default.
- W2567253913 creator A5024961589 @default.
- W2567253913 creator A5045335483 @default.
- W2567253913 creator A5063724302 @default.
- W2567253913 creator A5089510341 @default.
- W2567253913 date "2015-08-13" @default.
- W2567253913 modified "2023-09-27" @default.
- W2567253913 title "Abstract POSTER-TECH-1127: Genomic profiles inform treatment decisions and enable future drug/biomarker discovery" @default.
- W2567253913 doi "https://doi.org/10.1158/1557-3265.ovcasymp14-poster-tech-1127" @default.
- W2567253913 hasPublicationYear "2015" @default.
- W2567253913 type Work @default.
- W2567253913 sameAs 2567253913 @default.
- W2567253913 citedByCount "0" @default.
- W2567253913 crossrefType "proceedings-article" @default.
- W2567253913 hasAuthorship W2567253913A5024961589 @default.
- W2567253913 hasAuthorship W2567253913A5045335483 @default.
- W2567253913 hasAuthorship W2567253913A5063724302 @default.
- W2567253913 hasAuthorship W2567253913A5089510341 @default.
- W2567253913 hasConcept C104317684 @default.
- W2567253913 hasConcept C116567970 @default.
- W2567253913 hasConcept C121608353 @default.
- W2567253913 hasConcept C124535831 @default.
- W2567253913 hasConcept C126322002 @default.
- W2567253913 hasConcept C142724271 @default.
- W2567253913 hasConcept C143998085 @default.
- W2567253913 hasConcept C146357865 @default.
- W2567253913 hasConcept C150173356 @default.
- W2567253913 hasConcept C151730666 @default.
- W2567253913 hasConcept C163763905 @default.
- W2567253913 hasConcept C182979987 @default.
- W2567253913 hasConcept C190283241 @default.
- W2567253913 hasConcept C2777609662 @default.
- W2567253913 hasConcept C2779962180 @default.
- W2567253913 hasConcept C2780035454 @default.
- W2567253913 hasConcept C2781197716 @default.
- W2567253913 hasConcept C2781230642 @default.
- W2567253913 hasConcept C32220436 @default.
- W2567253913 hasConcept C46111723 @default.
- W2567253913 hasConcept C55493867 @default.
- W2567253913 hasConcept C60644358 @default.
- W2567253913 hasConcept C71924100 @default.
- W2567253913 hasConcept C82381507 @default.
- W2567253913 hasConcept C86554907 @default.
- W2567253913 hasConcept C86803240 @default.
- W2567253913 hasConcept C98274493 @default.
- W2567253913 hasConceptScore W2567253913C104317684 @default.
- W2567253913 hasConceptScore W2567253913C116567970 @default.
- W2567253913 hasConceptScore W2567253913C121608353 @default.
- W2567253913 hasConceptScore W2567253913C124535831 @default.
- W2567253913 hasConceptScore W2567253913C126322002 @default.
- W2567253913 hasConceptScore W2567253913C142724271 @default.
- W2567253913 hasConceptScore W2567253913C143998085 @default.
- W2567253913 hasConceptScore W2567253913C146357865 @default.
- W2567253913 hasConceptScore W2567253913C150173356 @default.
- W2567253913 hasConceptScore W2567253913C151730666 @default.
- W2567253913 hasConceptScore W2567253913C163763905 @default.
- W2567253913 hasConceptScore W2567253913C182979987 @default.
- W2567253913 hasConceptScore W2567253913C190283241 @default.
- W2567253913 hasConceptScore W2567253913C2777609662 @default.
- W2567253913 hasConceptScore W2567253913C2779962180 @default.
- W2567253913 hasConceptScore W2567253913C2780035454 @default.
- W2567253913 hasConceptScore W2567253913C2781197716 @default.
- W2567253913 hasConceptScore W2567253913C2781230642 @default.
- W2567253913 hasConceptScore W2567253913C32220436 @default.
- W2567253913 hasConceptScore W2567253913C46111723 @default.
- W2567253913 hasConceptScore W2567253913C55493867 @default.
- W2567253913 hasConceptScore W2567253913C60644358 @default.
- W2567253913 hasConceptScore W2567253913C71924100 @default.
- W2567253913 hasConceptScore W2567253913C82381507 @default.
- W2567253913 hasConceptScore W2567253913C86554907 @default.
- W2567253913 hasConceptScore W2567253913C86803240 @default.
- W2567253913 hasConceptScore W2567253913C98274493 @default.
- W2567253913 hasLocation W25672539131 @default.
- W2567253913 hasOpenAccess W2567253913 @default.
- W2567253913 hasPrimaryLocation W25672539131 @default.
- W2567253913 hasRelatedWork W1535004310 @default.
- W2567253913 hasRelatedWork W1963905418 @default.
- W2567253913 hasRelatedWork W2007724108 @default.
- W2567253913 hasRelatedWork W2012258551 @default.
- W2567253913 hasRelatedWork W2166310356 @default.
- W2567253913 hasRelatedWork W2237179606 @default.
- W2567253913 hasRelatedWork W2249215136 @default.
- W2567253913 hasRelatedWork W2314434958 @default.
- W2567253913 hasRelatedWork W2490701731 @default.
- W2567253913 hasRelatedWork W2604303638 @default.
- W2567253913 hasRelatedWork W2789246053 @default.
- W2567253913 hasRelatedWork W2792340731 @default.
- W2567253913 hasRelatedWork W2810037801 @default.
- W2567253913 hasRelatedWork W2944260190 @default.
- W2567253913 hasRelatedWork W2956155750 @default.
- W2567253913 hasRelatedWork W2980170966 @default.
- W2567253913 hasRelatedWork W3082001913 @default.
- W2567253913 hasRelatedWork W3163043083 @default.
- W2567253913 hasRelatedWork W3178683235 @default.
- W2567253913 hasRelatedWork W3212888956 @default.
- W2567253913 isParatext "false" @default.
- W2567253913 isRetracted "false" @default.
- W2567253913 magId "2567253913" @default.
- W2567253913 workType "article" @default.