Matches in SemOpenAlex for { <https://semopenalex.org/work/W3083489076> ?p ?o ?g. }
Showing items 1 to 82 of
82
with 100 items per page.
- W3083489076 abstract "Mouse double minute 2 homolog (MDM2) is E3 ubiquitin-protein ligase which facilitates proteasomal degradation of p53. MDM2 amplification has been reported in different tumor types and recently been implicated as a potential marker for accelerated tumor growth or hyperprogression in various types of cancer after receiving immune checkpoint inhibitors. Thus, targeting MDM2 might be a promising treatment strategy in the era of cancer immunotherapy especially for tumor with MDM2 amplification or overexpression that may be predisposed to hyperprogression after exposure to immune checkpoint therapy. To investigate the potential of targeting MDM2 strategy, we explored the role of inhibition of MDM2 by AMG-232, an investigational oral selective MDM2 inhibitor. MDM2-amplified and MDM2-non-amplified ovarian clear cell carcinoma cell lines carrying p53 wild-type were treated with AMG-232 and showed a dose-dependent reduction in cancer cell viability. MDM2 amplification showed more resistance to the treatment with AMG-232. Consistent with previous data, treatment with AMG-232 led to activation of the p53 signaling pathway in cancer cells in a dose-dependent manner. Importantly, the effect of MDM2 inhibition on cytokines expression was tested and significant reduction in Interleukin-6 (IL-6), a proinflammatory cytokine which promotes tumorigenesis by multiple signaling pathways, was observed in a dose-dependent manner. Ongoing experiments are examining the role of targeting MDM2 using AMG-232 in combination with immunotherapy, including the impact on killing of MDM2-amplified ovarian cancer cells by T-cells in the presence of immune checkpoint therapy. Overall, our data suggest a potential therapeutic role of targeting MDM2 especially in tumors with overexpression or amplification of MDM2 to overcome drug resistance including hyperprogression in the context of immune checkpoint therapy.Citation Format: Ilyas Sahin, Shengliang Zhang, Lanlan Zhou, Don Dizon, Howard Safran, Wafik S. El-Deiry. Targeting MDM2-amplified tumors with AMG-232 to overcome drug resistance, inflammatory pro-tumorigenic cytokine production and hyperprogression with immune checkpoint therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3009." @default.
- W3083489076 created "2020-09-11" @default.
- W3083489076 creator A5013039829 @default.
- W3083489076 creator A5036882735 @default.
- W3083489076 creator A5040266917 @default.
- W3083489076 creator A5064209980 @default.
- W3083489076 creator A5075201353 @default.
- W3083489076 creator A5078713649 @default.
- W3083489076 date "2020-08-13" @default.
- W3083489076 modified "2023-09-25" @default.
- W3083489076 title "Abstract 3009: Targeting MDM2-amplified tumors with AMG-232 to overcome drug resistance, inflammatory pro-tumorigenic cytokine production and hyperprogression with immune checkpoint therapy" @default.
- W3083489076 doi "https://doi.org/10.1158/1538-7445.am2020-3009" @default.
- W3083489076 hasPublicationYear "2020" @default.
- W3083489076 type Work @default.
- W3083489076 sameAs 3083489076 @default.
- W3083489076 citedByCount "0" @default.
- W3083489076 crossrefType "proceedings-article" @default.
- W3083489076 hasAuthorship W3083489076A5013039829 @default.
- W3083489076 hasAuthorship W3083489076A5036882735 @default.
- W3083489076 hasAuthorship W3083489076A5040266917 @default.
- W3083489076 hasAuthorship W3083489076A5064209980 @default.
- W3083489076 hasAuthorship W3083489076A5075201353 @default.
- W3083489076 hasAuthorship W3083489076A5078713649 @default.
- W3083489076 hasConcept C104317684 @default.
- W3083489076 hasConcept C121608353 @default.
- W3083489076 hasConcept C126322002 @default.
- W3083489076 hasConcept C134459356 @default.
- W3083489076 hasConcept C164027704 @default.
- W3083489076 hasConcept C203014093 @default.
- W3083489076 hasConcept C25602115 @default.
- W3083489076 hasConcept C2776192174 @default.
- W3083489076 hasConcept C2776914184 @default.
- W3083489076 hasConcept C2777701055 @default.
- W3083489076 hasConcept C2778690821 @default.
- W3083489076 hasConcept C2780851360 @default.
- W3083489076 hasConcept C502942594 @default.
- W3083489076 hasConcept C54355233 @default.
- W3083489076 hasConcept C55493867 @default.
- W3083489076 hasConcept C555283112 @default.
- W3083489076 hasConcept C71924100 @default.
- W3083489076 hasConcept C81885089 @default.
- W3083489076 hasConcept C86803240 @default.
- W3083489076 hasConcept C8891405 @default.
- W3083489076 hasConcept C96232424 @default.
- W3083489076 hasConceptScore W3083489076C104317684 @default.
- W3083489076 hasConceptScore W3083489076C121608353 @default.
- W3083489076 hasConceptScore W3083489076C126322002 @default.
- W3083489076 hasConceptScore W3083489076C134459356 @default.
- W3083489076 hasConceptScore W3083489076C164027704 @default.
- W3083489076 hasConceptScore W3083489076C203014093 @default.
- W3083489076 hasConceptScore W3083489076C25602115 @default.
- W3083489076 hasConceptScore W3083489076C2776192174 @default.
- W3083489076 hasConceptScore W3083489076C2776914184 @default.
- W3083489076 hasConceptScore W3083489076C2777701055 @default.
- W3083489076 hasConceptScore W3083489076C2778690821 @default.
- W3083489076 hasConceptScore W3083489076C2780851360 @default.
- W3083489076 hasConceptScore W3083489076C502942594 @default.
- W3083489076 hasConceptScore W3083489076C54355233 @default.
- W3083489076 hasConceptScore W3083489076C55493867 @default.
- W3083489076 hasConceptScore W3083489076C555283112 @default.
- W3083489076 hasConceptScore W3083489076C71924100 @default.
- W3083489076 hasConceptScore W3083489076C81885089 @default.
- W3083489076 hasConceptScore W3083489076C86803240 @default.
- W3083489076 hasConceptScore W3083489076C8891405 @default.
- W3083489076 hasConceptScore W3083489076C96232424 @default.
- W3083489076 hasLocation W30834890761 @default.
- W3083489076 hasOpenAccess W3083489076 @default.
- W3083489076 hasPrimaryLocation W30834890761 @default.
- W3083489076 hasRelatedWork W1183554201 @default.
- W3083489076 hasRelatedWork W2065690661 @default.
- W3083489076 hasRelatedWork W2979186475 @default.
- W3083489076 hasRelatedWork W3040650435 @default.
- W3083489076 hasRelatedWork W3083489076 @default.
- W3083489076 hasRelatedWork W4283731173 @default.
- W3083489076 hasRelatedWork W4291367166 @default.
- W3083489076 hasRelatedWork W4297883870 @default.
- W3083489076 hasRelatedWork W4353109719 @default.
- W3083489076 hasRelatedWork W4360983034 @default.
- W3083489076 isParatext "false" @default.
- W3083489076 isRetracted "false" @default.
- W3083489076 magId "3083489076" @default.
- W3083489076 workType "article" @default.