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Evaluation of the Antitumor Effects and Mechanisms of PF00299804, a Pan-HER Inhibitor, Alone or in Combination with Chemotherapy or Targeted Agents in Gastric Cancer
DC Field | Value | Language |
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dc.contributor.author | Nam, Hyun-Jin | - |
dc.contributor.author | Ching, Keith A. | - |
dc.contributor.author | Kan, Julie | - |
dc.contributor.author | Kim, Hwang-Phill | - |
dc.contributor.author | Han, Sae-Won | - |
dc.contributor.author | Im, Seock-Ah | - |
dc.contributor.author | Kim, Tae-You | - |
dc.contributor.author | Christensen, James G. | - |
dc.contributor.author | Oh, Do-Youn | - |
dc.contributor.author | Bang, Yung-Jue | - |
dc.date.accessioned | 2021-01-31T12:03:31Z | - |
dc.date.available | 2021-01-31T12:03:31Z | - |
dc.date.created | 2020-08-20 | - |
dc.date.created | 2020-08-20 | - |
dc.date.created | 2020-08-20 | - |
dc.date.created | 2020-08-20 | - |
dc.date.issued | 2012-02 | - |
dc.identifier.citation | Molecular Cancer Therapeutics, Vol.11 No.2, pp.439-451 | - |
dc.identifier.issn | 1535-7163 | - |
dc.identifier.other | 111064 | - |
dc.identifier.uri | https://hdl.handle.net/10371/173240 | - |
dc.description.abstract | Recently, HER2-directed treatment, such as trastuzumab, has shown clinical benefit in HER2-amplified gastric cancer. On the basis of recent studies about epidermal growth factor receptor (EGFR) or HER2-targeting agents (including gefitinib, lapatinib, and trastuzumab) in gastric cancer, the potent effects of pan-HER inhibitors targeting the HER family are anticipated. In this study, we evaluated the activity and mechanisms of PF00299804, an irreversible pan-HER inhibitor, in gastric cancer in vitro and in vivo models. PF00299804 showed significant growth-inhibitory effects in HER2-amplified gastric cancer cells (SNU216, N87), and it had lower 50% inhibitory concentration values compared with other EGFR tyrosine kinase inhibitors, including gefitinib, lapatinib, BIBW-2992, and CI-1033. PF00299804 induced apoptosis and G1 arrest and inhibited phosphorylation of receptors in the HER family and downstream signaling pathways including STAT3, AKT, and extracellular signal-regulated kinases (ERK) in HER2-amplified gastric cancer cells. PF00299804 also blocked EGFR/HER2, HER2/HER3, and HER3/HER4 heterodimer formation as well as the association of HER3 with p85 alpha in SNU216 cells. The combination of PF00299804 with clinically relevant chemotherapeutic agents or molecular-targeted agents including trastuzumab (an anti-HER2 monoclonal antibody), CP751871 (an IGF1R inhibitor), PD0325901 (an ERK1/2 inhibitor), and PF04691502 (a PI3K/mTOR inhibitor) produced synergistic effects. These findings indicate that PF00299804 can be used as a targeted therapy for the treatment of HER2-amplified gastric cancer through inhibition of HER family heterodimer formation and may augment antitumor efficacy of chemotherapeutic and/or molecular-targeted agents. Mol Cancer Ther; 11(2); 439-51. (C) 2011 AACR. | - |
dc.language | 영어 | - |
dc.publisher | American Association for Cancer Research | - |
dc.title | Evaluation of the Antitumor Effects and Mechanisms of PF00299804, a Pan-HER Inhibitor, Alone or in Combination with Chemotherapy or Targeted Agents in Gastric Cancer | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 임석아 | - |
dc.identifier.doi | 10.1158/1535-7163.MCT-11-0494 | - |
dc.citation.journaltitle | Molecular Cancer Therapeutics | - |
dc.identifier.wosid | 000300415300018 | - |
dc.identifier.scopusid | 2-s2.0-84863169318 | - |
dc.citation.endpage | 451 | - |
dc.citation.number | 2 | - |
dc.citation.startpage | 439 | - |
dc.citation.volume | 11 | - |
dc.identifier.sci | 000300415300018 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Im, Seock-Ah | - |
dc.contributor.affiliatedAuthor | Kim, Tae-You | - |
dc.contributor.affiliatedAuthor | Oh, Do-Youn | - |
dc.contributor.affiliatedAuthor | Bang, Yung-Jue | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | TYROSINE KINASE INHIBITOR | - |
dc.subject.keywordPlus | BREAST-CANCER | - |
dc.subject.keywordPlus | MONOCLONAL-ANTIBODY | - |
dc.subject.keywordPlus | DUAL EGFR | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | GROWTH | - |
dc.subject.keywordPlus | LUNG | - |
dc.subject.keywordPlus | LAPATINIB | - |
dc.subject.keywordPlus | OVEREXPRESSION | - |
dc.subject.keywordPlus | TRASTUZUMAB | - |
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