Matches in SemOpenAlex for { <https://semopenalex.org/work/W4362541796> ?p ?o ?g. }
Showing items 1 to 70 of
70
with 100 items per page.
- W4362541796 abstract "<div>Abstract<p>Lung cancer is the leading cause of cancer-related deaths with small-cell lung cancer (SCLC) as the most aggressive subtype. Preferential occurrence of TP53 missense mutations rather than loss implicates a selective advantage for TP53-mutant expression in SCLC pathogenesis. We show that lung epithelial expression of R270H and R172H (R273H and R175H in humans), common TRP53 mutants in lung cancer, combined with RB1 loss selectively results in two subtypes of neuroendocrine carcinoma, SCLC and large cell neuroendocrine carcinoma (LCNEC). Tumor initiation and progression occur in a remarkably consistent time frame with short latency and uniform progression to lethal metastatic disease by 7 months. R270H or R172H expression and TRP53 loss result in similar phenotypes demonstrating that TRP53 mutants promote lung carcinogenesis through loss-of-function and not gain-of-function mechanisms. Tumor responses to targeted and cytotoxic therapeutics were discordant in mice and corresponding tumor cell cultures demonstrating need to assess therapeutic response at the organismal level. Rapamycin did not have therapeutic efficacy in the mouse model despite inhibiting mTOR signaling and markedly suppressing tumor cell growth in culture. In contrast, cisplatin/etoposide treatment using a patient regimen prolonged survival with development of chemoresistance recapitulating human responses. R270H, but not R172H, expression conferred gain-of-function activity in attenuating chemotherapeutic efficacy. These data demonstrate a causative role for TRP53 mutants in development of chemoresistant lung cancer, and provide tractable preclinical models to test novel therapeutics for refractory disease. <i>Mol Cancer Ther; 16(12); 2913–26. ©2017 AACR</i>.</p></div>" @default.
- W4362541796 created "2023-04-06" @default.
- W4362541796 creator A5008149235 @default.
- W4362541796 creator A5014582092 @default.
- W4362541796 creator A5017066806 @default.
- W4362541796 creator A5019140574 @default.
- W4362541796 creator A5029343978 @default.
- W4362541796 creator A5051070674 @default.
- W4362541796 creator A5066612645 @default.
- W4362541796 creator A5078083620 @default.
- W4362541796 creator A5088593405 @default.
- W4362541796 date "2023-04-03" @default.
- W4362541796 modified "2023-10-14" @default.
- W4362541796 title "Data from TRP53 Mutants Drive Neuroendocrine Lung Cancer Through Loss-of-Function Mechanisms with Gain-of-Function Effects on Chemotherapy Response" @default.
- W4362541796 doi "https://doi.org/10.1158/1535-7163.c.6537954.v1" @default.
- W4362541796 hasPublicationYear "2023" @default.
- W4362541796 type Work @default.
- W4362541796 citedByCount "0" @default.
- W4362541796 crossrefType "posted-content" @default.
- W4362541796 hasAuthorship W4362541796A5008149235 @default.
- W4362541796 hasAuthorship W4362541796A5014582092 @default.
- W4362541796 hasAuthorship W4362541796A5017066806 @default.
- W4362541796 hasAuthorship W4362541796A5019140574 @default.
- W4362541796 hasAuthorship W4362541796A5029343978 @default.
- W4362541796 hasAuthorship W4362541796A5051070674 @default.
- W4362541796 hasAuthorship W4362541796A5066612645 @default.
- W4362541796 hasAuthorship W4362541796A5078083620 @default.
- W4362541796 hasAuthorship W4362541796A5088593405 @default.
- W4362541796 hasConcept C104317684 @default.
- W4362541796 hasConcept C121608353 @default.
- W4362541796 hasConcept C127716648 @default.
- W4362541796 hasConcept C142724271 @default.
- W4362541796 hasConcept C2776256026 @default.
- W4362541796 hasConcept C2776694085 @default.
- W4362541796 hasConcept C2778119113 @default.
- W4362541796 hasConcept C2779256057 @default.
- W4362541796 hasConcept C502942594 @default.
- W4362541796 hasConcept C54355233 @default.
- W4362541796 hasConcept C555283112 @default.
- W4362541796 hasConcept C71924100 @default.
- W4362541796 hasConcept C86803240 @default.
- W4362541796 hasConceptScore W4362541796C104317684 @default.
- W4362541796 hasConceptScore W4362541796C121608353 @default.
- W4362541796 hasConceptScore W4362541796C127716648 @default.
- W4362541796 hasConceptScore W4362541796C142724271 @default.
- W4362541796 hasConceptScore W4362541796C2776256026 @default.
- W4362541796 hasConceptScore W4362541796C2776694085 @default.
- W4362541796 hasConceptScore W4362541796C2778119113 @default.
- W4362541796 hasConceptScore W4362541796C2779256057 @default.
- W4362541796 hasConceptScore W4362541796C502942594 @default.
- W4362541796 hasConceptScore W4362541796C54355233 @default.
- W4362541796 hasConceptScore W4362541796C555283112 @default.
- W4362541796 hasConceptScore W4362541796C71924100 @default.
- W4362541796 hasConceptScore W4362541796C86803240 @default.
- W4362541796 hasLocation W43625417961 @default.
- W4362541796 hasOpenAccess W4362541796 @default.
- W4362541796 hasPrimaryLocation W43625417961 @default.
- W4362541796 hasRelatedWork W2008017868 @default.
- W4362541796 hasRelatedWork W2069273774 @default.
- W4362541796 hasRelatedWork W2116762030 @default.
- W4362541796 hasRelatedWork W2192248769 @default.
- W4362541796 hasRelatedWork W2487824964 @default.
- W4362541796 hasRelatedWork W2560940732 @default.
- W4362541796 hasRelatedWork W2769390123 @default.
- W4362541796 hasRelatedWork W2803210216 @default.
- W4362541796 hasRelatedWork W3025716972 @default.
- W4362541796 hasRelatedWork W3131644024 @default.
- W4362541796 isParatext "false" @default.
- W4362541796 isRetracted "false" @default.
- W4362541796 workType "article" @default.