DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Koh, Gou Young | - |
dc.contributor.advisor | 고규영 | - |
dc.contributor.advisor | Lee, Dae Ho | - |
dc.contributor.advisor | 이대호 | - |
dc.contributor.author | Yang, Hanna | - |
dc.date.accessioned | 2019-08-25T02:43:33Z | - |
dc.date.available | 2019-08-25T02:43:33Z | - |
dc.date.issued | 2018 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=734376&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/265108 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 의과학학제전공, 2018.2,[v, 57 p. :] | - |
dc.description.abstract | Small cell lung cancer (SCLC) cannot be efficiently controlled using existing chemotherapy and radiotherapy approaches, indicating the need for new therapeutic strategies. Although ABT-737, a B-cell lymphoma-2 (BCL-2) inhibitor, exerts anti-cancer effects against BCL-2-expressing SCLC, monotherapy with ABT-737 is associated with limited clinical activity because of the development of resistance and toxicity. Here, we examined whether combination therapy with ABT-737 and heat shock protein 90 (HSP90) inhibitor NVP-AUY922 exerted synergistic anti-cancer effects on SCLC. We found that the combination of ABT-737 and NVP-AUY922 synergistically induced the apoptosis of BCL-2-expressing SCLC cells. NVP-AUY922 downregulated the expression of AKT and ERK, which activate MCL-1 to induce resistance against ABT-737. The synergistic effect was also partly due to blocking NF-κB activation, which induces anti-apoptosis protein expressions. However, interestingly, targeting BCL-2 and MCL-1 or BCL-2 and NF-κB did not induce the cytotoxicity. In conclusion, our study showed that combination of BCL-2 inhibitor with HSP90 inhibitor increased activity in in vitro and in vivo study in only BCL-2 expressing SCLC compared to either single BCL-2 inhibitor or HSP inhibitor. The enhanced activity might be led by blocking several apoptotic pathways simultaneously rather than a specific pathway. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | small cell lung cancer▼aBCL-2 inhibitor▼aHSP90 inhibitor▼acombination therapy▼asynergy effect | - |
dc.subject | 소세포폐암▼aBCL-2억제제▼aHSP90억제제▼a병용사용▼a시너지효과 | - |
dc.title | (The) mechanism of HSP90 inhibitor in enhancing the anti-cancer effects of BCL-2 inhibitor in small cell lung cancer | - |
dc.title.alternative | 소세포폐암에서 BCL-2억제제 항암효과를 향상시키는 HSP90억제제 기전 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :의과학학제전공, | - |
dc.contributor.alternativeauthor | 양한나 | - |
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