Matches in SemOpenAlex for { <https://semopenalex.org/work/W2476345746> ?p ?o ?g. }
Showing items 1 to 82 of
82
with 100 items per page.
- W2476345746 abstract "Subsets of uterine serous carcinomas (USC) harbor simultaneous HER2 (ERBB2) over-expression and gain of function mutations in PIK3CA that may play a role in resistance to single agent anti-HER2 therapies. Targeting the mammalian target of rapamycin (mTOR) may be a promising option to heighten anti-tumor response and restore sensitivity to anti-HER2 therapies. HER2 gene amplified cell lines with (ARK1, E542K) and without (ARK2) PIK3CA gene mutations were divided into four arm cohorts with equivalent tumor volumes and treated with either vehicle, ridaforolimus (1 mg/kg, lapatinib (150 mg/kg) and trastuzumab (10mg/kg) or the combination of lapatinib/trastuzumab and ridaforolimus. At day 22, tumors were collected to measure downstream target proteins and calculate the proliferation and apoptosis index. In the ARK1 USC xenograft cohort, inhibition of tumor growth was observed following treatment with ridaforolimus compared to vehicle (P Analysis of the treatment effects revealed the lapatinib/trastuzumab/ridaforolimus therapy was required to decrease Ki67 positive cells in ARK1 xenografts compared to the vehicle (P These data suggest that USCs harboring gain of function PIK3CA mutations are relatively insensitive to anti-HER2 therapies. The addition of downstream mTOR inhibition to HER2 blockade increased the anti-tumor activity only in the xenograft model with PIK3CA mutation and provides rationale for clinical trials in HER2 positive endometrial cancers based on molecular genotype. Citation Format: Silvia F. Hernandez, Sarah Chisholm, Darrell Borger, Rosemary Foster, Bo R. Rueda, Whitfield B. Growdon. Addition of mTOR inhibition to HER2 blockade results in improved antitumor activity in a preclinical model of uterine serous carcinoma with HER2 gene amplification and a gain of function mutation in PIK3CA. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 386." @default.
- W2476345746 created "2016-08-23" @default.
- W2476345746 creator A5013180518 @default.
- W2476345746 creator A5014287583 @default.
- W2476345746 creator A5045933687 @default.
- W2476345746 creator A5053081492 @default.
- W2476345746 creator A5060473465 @default.
- W2476345746 creator A5088371009 @default.
- W2476345746 date "2016-07-15" @default.
- W2476345746 modified "2023-09-25" @default.
- W2476345746 title "Abstract 386: Addition of mTOR inhibition to HER2 blockade results in improved antitumor activity in a preclinical model of uterine serous carcinoma with HER2 gene amplification and a gain of function mutation in PIK3CA" @default.
- W2476345746 doi "https://doi.org/10.1158/1538-7445.am2016-386" @default.
- W2476345746 hasPublicationYear "2016" @default.
- W2476345746 type Work @default.
- W2476345746 sameAs 2476345746 @default.
- W2476345746 citedByCount "0" @default.
- W2476345746 crossrefType "proceedings-article" @default.
- W2476345746 hasAuthorship W2476345746A5013180518 @default.
- W2476345746 hasAuthorship W2476345746A5014287583 @default.
- W2476345746 hasAuthorship W2476345746A5045933687 @default.
- W2476345746 hasAuthorship W2476345746A5053081492 @default.
- W2476345746 hasAuthorship W2476345746A5060473465 @default.
- W2476345746 hasAuthorship W2476345746A5088371009 @default.
- W2476345746 hasConcept C121608353 @default.
- W2476345746 hasConcept C126322002 @default.
- W2476345746 hasConcept C143998085 @default.
- W2476345746 hasConcept C170493617 @default.
- W2476345746 hasConcept C190283241 @default.
- W2476345746 hasConcept C2777329042 @default.
- W2476345746 hasConcept C2778468042 @default.
- W2476345746 hasConcept C2779707156 @default.
- W2476345746 hasConcept C2779786085 @default.
- W2476345746 hasConcept C502942594 @default.
- W2476345746 hasConcept C530470458 @default.
- W2476345746 hasConcept C54355233 @default.
- W2476345746 hasConcept C71924100 @default.
- W2476345746 hasConcept C86554907 @default.
- W2476345746 hasConcept C86803240 @default.
- W2476345746 hasConcept C98274493 @default.
- W2476345746 hasConceptScore W2476345746C121608353 @default.
- W2476345746 hasConceptScore W2476345746C126322002 @default.
- W2476345746 hasConceptScore W2476345746C143998085 @default.
- W2476345746 hasConceptScore W2476345746C170493617 @default.
- W2476345746 hasConceptScore W2476345746C190283241 @default.
- W2476345746 hasConceptScore W2476345746C2777329042 @default.
- W2476345746 hasConceptScore W2476345746C2778468042 @default.
- W2476345746 hasConceptScore W2476345746C2779707156 @default.
- W2476345746 hasConceptScore W2476345746C2779786085 @default.
- W2476345746 hasConceptScore W2476345746C502942594 @default.
- W2476345746 hasConceptScore W2476345746C530470458 @default.
- W2476345746 hasConceptScore W2476345746C54355233 @default.
- W2476345746 hasConceptScore W2476345746C71924100 @default.
- W2476345746 hasConceptScore W2476345746C86554907 @default.
- W2476345746 hasConceptScore W2476345746C86803240 @default.
- W2476345746 hasConceptScore W2476345746C98274493 @default.
- W2476345746 hasLocation W24763457461 @default.
- W2476345746 hasOpenAccess W2476345746 @default.
- W2476345746 hasPrimaryLocation W24763457461 @default.
- W2476345746 hasRelatedWork W1535531465 @default.
- W2476345746 hasRelatedWork W1567668080 @default.
- W2476345746 hasRelatedWork W1746121681 @default.
- W2476345746 hasRelatedWork W1827534589 @default.
- W2476345746 hasRelatedWork W1971872502 @default.
- W2476345746 hasRelatedWork W1989833665 @default.
- W2476345746 hasRelatedWork W2038858233 @default.
- W2476345746 hasRelatedWork W2055626163 @default.
- W2476345746 hasRelatedWork W2106301124 @default.
- W2476345746 hasRelatedWork W2126065672 @default.
- W2476345746 hasRelatedWork W2317336722 @default.
- W2476345746 hasRelatedWork W2318101903 @default.
- W2476345746 hasRelatedWork W2339832066 @default.
- W2476345746 hasRelatedWork W2408289233 @default.
- W2476345746 hasRelatedWork W2562570560 @default.
- W2476345746 hasRelatedWork W2598021891 @default.
- W2476345746 hasRelatedWork W2666473733 @default.
- W2476345746 hasRelatedWork W2741845033 @default.
- W2476345746 hasRelatedWork W2977904080 @default.
- W2476345746 hasRelatedWork W3177808128 @default.
- W2476345746 isParatext "false" @default.
- W2476345746 isRetracted "false" @default.
- W2476345746 magId "2476345746" @default.
- W2476345746 workType "article" @default.