Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention
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 precl...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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2020
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| Online Access: | https://hdl.handle.net/1721.1/125700 |
| _version_ | 1826208430333886464 |
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| author | 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 |
| author2 | Singapore-MIT Alliance in Research and Technology (SMART) |
| author_facet | Singapore-MIT Alliance in Research and Technology (SMART) 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 |
| author_sort | Khoo, Bee Luan |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:05:39Z |
| format | Article |
| id | mit-1721.1/125700 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:05:39Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | mit-1721.1/1257002022-10-01T19:10:28Z 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 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 Singapore-MIT Alliance in Research and Technology (SMART) Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology. Department of Biological Engineering 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. Singapore. National Medical Research Council (Grant NMRC) 2020-06-05T19:56:58Z 2020-06-05T19:56:58Z 2019-02 2018-09 2019-06-05T16:10:43Z Article http://purl.org/eprint/type/JournalArticle 0007-0920 1532-1827 https://hdl.handle.net/1721.1/125700 Khoo, Bee Luan, Gianluca Grenci, Joey Sze Yun Lim et al. "Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention." British Journal of Cancer (February 2019) 120:407-423 © 2019, The Author(s). en https://dx.doi.org/10.1038/s41416-018-0301-9 British Journal of Cancer Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Nature |
| spellingShingle | 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 Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention |
| title | Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention |
| title_full | Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention |
| title_fullStr | Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention |
| title_full_unstemmed | Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention |
| title_short | Low-dose anti-inflammatory combinatorial therapy reduced cancer stem cell formation in patient-derived preclinical models for tumour relapse prevention |
| title_sort | low dose anti inflammatory combinatorial therapy reduced cancer stem cell formation in patient derived preclinical models for tumour relapse prevention |
| url | https://hdl.handle.net/1721.1/125700 |
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