Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Gianluca Grenci
  • Joey Sze Yun Lim
  • Yan Ping Lim
  • July Fong
  • Wei Hseun Yeap
  • Su Bin Lim
  • Song Lin Chua
  • Siew Cheng Wong
  • Yoon-Sim Yap
  • Soo Chin Lee
  • Chwee Teck Lim
  • Jongyoon Han

Detail(s)

Original languageEnglish
Pages (from-to)407-423
Journal / PublicationBritish Journal of Cancer
Volume120
Issue number4
Online published4 Feb 2019
Publication statusPublished - 19 Feb 2019
Externally publishedYes

Link(s)

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.

Research Area(s)

Citation Format(s)

Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention. / Khoo, Bee Luan; Grenci, Gianluca; Lim, Joey Sze Yun et al.
In: British Journal of Cancer, Vol. 120, No. 4, 19.02.2019, p. 407-423.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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