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Title: Improving the therapeutic ratio of radiotherapy against radioresistant cancers: Leveraging on novel artificial intelligence-based approaches for drug combination discovery
Authors: Poon, Dennis Jun Jie
Tay, Li Min 
Ho, Dean 
Chua, Melvin Lee Kiang 
Chow, Edward Kai-Hua 
Yeo, Eugenia Li Ling
Keywords: Artificial intelligence
Cancer radioresistance
Combinatorial therapeutics
Drug development
Machine learning
Issue Date: 1-Jul-2021
Publisher: Elsevier Ireland Ltd
Citation: Poon, Dennis Jun Jie, Tay, Li Min, Ho, Dean, Chua, Melvin Lee Kiang, Chow, Edward Kai-Hua, Yeo, Eugenia Li Ling (2021-07-01). Improving the therapeutic ratio of radiotherapy against radioresistant cancers: Leveraging on novel artificial intelligence-based approaches for drug combination discovery. Cancer Letters 511 : 56-67. ScholarBank@NUS Repository.
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
Abstract: Despite numerous advances in cancer radiotherapy, tumor radioresistance remain one of the major challenges limiting treatment efficacy of radiotherapy. Conventional strategies to overcome radioresistance involve understanding the underpinning molecular mechanisms, and subsequently using combinatorial treatment strategies involving radiation and targeted drug combinations against these radioresistant tumors. These strategies exploit and target the molecular fingerprint and vulnerability of the radioresistant clones to achieve improved efficacy in tumor eradication. However, conventional drug-screening approaches for the discovery of new drug combinations have been proven to be inefficient, limited and laborious. With the increasing availability of computational resources in recent years, novel approaches such as Quadratic Phenotypic Optimization Platform (QPOP), CURATE.AI and Drug Combination and Prediction and Testing (DCPT) platform have emerged to aid in drug combination discovery and the longitudinally optimized modulation of combination therapy dosing. These platforms could overcome the limitations of conventional screening approaches, thereby facilitating the discovery of more optimal drug combinations to improve the therapeutic ratio of combinatorial treatment. The use of better and more accurate models and methods with rapid turnover can thus facilitate a rapid translation in the clinic, hence, resulting in a better patient outcome. Here, we reviewed the clinical observations, molecular mechanisms and proposed treatment strategies for tumor radioresistance and discussed how novel approaches may be applied to enhance drug combination discovery, with the aim to further improve the therapeutic ratio and treatment efficacy of radiotherapy against radioresistant cancers. © 2021 The Authors
Source Title: Cancer Letters
ISSN: 0304-3835
DOI: 10.1016/j.canlet.2021.04.019
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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