Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41416-018-0301-9
Title: Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention
Authors: Khoo, Bee Luan
Grenci, Gianluca 
Lim, Joey Sze Yun
Lim, Yan Ping 
Fong, July
Yeap, Wei Hseun
Lim, Su Bin
Chua, Song Lin
Wong, Siew Cheng 
Yap, Yoon-Sim 
Lee, Soo Chin 
Lim, Chwee Teck 
Han, Jongyoon
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
EPITHELIAL-MESENCHYMAL TRANSITION
BREAST-CANCER
COLORECTAL-CANCER
INDUCE APOPTOSIS
DRUG-RESISTANCE
CARCINOMA CELLS
GASTRIC-CANCER
IN-VITRO
ASPIRIN
RISK
Issue Date: 19-Feb-2019
Publisher: NATURE PUBLISHING GROUP
Citation: Khoo, Bee Luan, Grenci, Gianluca, Lim, Joey Sze Yun, Lim, Yan Ping, Fong, July, Yeap, Wei Hseun, Lim, Su Bin, Chua, Song Lin, Wong, Siew Cheng, Yap, Yoon-Sim, Lee, Soo Chin, Lim, Chwee Teck, Han, Jongyoon (2019-02-19). Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention. BRITISH JOURNAL OF CANCER 120 (4) : 407-423. ScholarBank@NUS Repository. https://doi.org/10.1038/s41416-018-0301-9
Abstract: Background: Emergence of drug-resistant cancer phenotypes is a challenge for anti-cancer therapy. Cancer stem cells are identified as one of the ways by which chemoresistance develops. Method: We investigated the anti-inflammatory combinatorial treatment (DA) of doxorubicin and aspirin using a preclinical microfluidic model on cancer cell lines and patient-derived circulating tumour cell clusters. The model had been previously demonstrated to predict patient overall prognosis. Results: We demonstrated that low-dose aspirin with a sub-optimal dose of doxorubicin for 72 h could generate higher killing efficacy and enhanced apoptosis. Seven days of DA treatment significantly reduced the proportion of cancer stem cells and colony-forming ability. DA treatment delayed the inhibition of interleukin-6 secretion, which is mediated by both COX-dependent and independent pathways. The response of patients varied due to clinical heterogeneity, with 62.5% and 64.7% of samples demonstrating higher killing efficacy or reduction in cancer stem cell (CSC) proportions after DA treatment, respectively. These results highlight the importance of using patient-derived models for drug discovery. Conclusions: This preclinical proof of concept seeks to reduce the onset of CSCs generated post treatment by stressful stimuli. Our study will promote a better understanding of anti-inflammatory treatments for cancer and reduce the risk of relapse in patients.
Source Title: BRITISH JOURNAL OF CANCER
URI: https://scholarbank.nus.edu.sg/handle/10635/239146
ISSN: 0007-0920
1532-1827
DOI: 10.1038/s41416-018-0301-9
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention.pdfPublished version4.65 MBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.