Identification of pancreatic cancer stem cell and its targeting molecule = 췌장암 종양줄기세포의 확인 및 표적 치료물질의 개발

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Human pancreatic ductal adenocarcinoma (PDAC) is a cancer with a dismal prognosis. The efficacy of PDAC anticancer therapies is often short-lived; however, there is little information on how this disease entity so frequently gains resistance to treatment. I adopted the concept of cancer stem cells (CSCs) to explain the mechanism of resistance and evaluated the efficacy of a candidate anticancer drug to target these therapy-resistant CSCs. I identified a subpopulation of cells in PDAC with CSC features that were enriched for aldehyde dehydrogenase (ALDH), a marker expressed in certain stem/progenitor cells. These cells were also highly resistant to, and were further enriched by, treatment with gemcitabine. Similarly, surgical specimens from PDAC patients showed that those who had undergone preoperative chemo-radiation therapy more frequently displayed cancers with ALDH strongly positive subpopulations compared with untreated patients. Importantly, these ALDH-high cancer cells were sensitive to disulfiram, an ALDH inhibitor, when tested in vitro. Furthermore, in vivo xenograft studies showed that the effect of disulfiram was additive to that of low-dose gemcitabine when applied in combination. In conclusion, human PDAC-derived cells that express high levels of ALDH show CSC features and have a key role in the development of resistance to anticancer therapies. Disulfiram can be used to suppress this therapy-resistant subpopulation.
Advisors
Lim, Dae-Sikresearcher임대식
Description
한국과학기술원 : 의과학대학원,
Publisher
한국과학기술원
Issue Date
2013
Identifier
565598/325007  / 020105227
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 의과학대학원, 2013.8, [ vi, 92 p. ]

Keywords

pancreatic cancer; 디설피람; 아세트알데하이드 탈수효소; 치료 저항성; 췌장암; disulfiram; therapy-resistance; ADLH

URI
http://hdl.handle.net/10203/197756
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=565598&flag=dissertation
Appears in Collection
MSE-Theses_Ph.D.(박사논문)
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