Publications by authors named "Tzen S Toh"

Article Synopsis
  • Drug resistance poses a major obstacle to cancer treatments, with drug-tolerant 'persister' (DTP) cells playing a key role in this resistance.
  • DTP cells exhibit high plasticity and can shift between different states, leading to various phenotypes in tumors, but their specific biological characteristics are still not fully understood.
  • The study aims to review existing knowledge about DTPs while suggesting future research directions and potential strategies to target and eliminate these cells in order to improve treatment outcomes.
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Background & Purpose: Prophylactic cranial irradiation (PCI) is recommended for limited-stage small-cell lung cancer (LS-SCLC) patients with good response to concurrent chemoradiation. We report our institution's 20-year experience with this patient population and associated clinical outcomes.

Materials & Methods: A retrospective cohort of consecutive LS-SCLC patients treated with curative intent chemoradiation at our institution (1997-2018) was reviewed.

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Article Synopsis
  • Despite twice-daily radiotherapy schedules being generally better, their practical use is complicated, leading to the adoption of hypofractionated radiotherapy (HFRT) as an alternative.
  • A study compared outcomes and toxicities in patients with limited-stage small-cell lung cancer treated with either twice-daily or hypofractionated schedules from 2007 to 2019.
  • The analysis of 173 patients showed no significant differences in overall survival, locoregional recurrence, or severe toxicity between the two treatment methods.
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High-throughput testing of drugs across molecular-characterised cell lines can identify candidate treatments and discover biomarkers. However, the cells' response to a drug is typically quantified by a summary statistic from a best-fit dose-response curve, whilst neglecting the uncertainty of the curve fit and the potential variability in the raw readouts. Here, we model the experimental variance using Gaussian Processes, and subsequently, leverage uncertainty estimates to identify associated biomarkers with a new Bayesian framework.

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Personalised medicine has predominantly focused on genetically altered cancer genes that stratify drug responses, but there is a need to objectively evaluate differential pharmacology patterns at a subpopulation level. Here, we introduce an approach based on unsupervised machine learning to compare the pharmacological response relationships between 327 pairs of cancer therapies. This approach integrated multiple measures of response to identify subpopulations that react differently to inhibitors of the same or different targets to understand mechanisms of resistance and pathway cross-talk.

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Big data problems are becoming more prevalent for laboratory scientists who look to make clinical impact. A large part of this is due to increased computing power, in parallel with new technologies for high quality data generation. Both new and old techniques of artificial intelligence (AI) and machine learning (ML) can now help increase the success of translational studies in three areas: drug discovery, imaging, and genomic medicine.

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