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Longitudinal tumour volume data from head-and-neck cancer patients show that tumours of comparable pre-treatment size and stage may respond very differently to the same radiotherapy fractionation protocol. Mathematical models are often proposed to predict treatment outcome in this context, and have the potential to guide clinical decision-making and inform personalised fractionation protocols. Hindering effective use of models in this context is the sparsity of clinical measurements juxtaposed with the model complexity required to produce the full range of possible patient responses. In this work, we present a compartment model of tumour volume and tumour composition, which, despite relative simplicity, is capable of producing a wide range of patient responses. We then develop novel statistical methodology and leverage a cohort of existing clinical data to produce a predictive model of both tumour volume progression and the associated level of uncertainty that evolves throughout a patient's course of treatment. To capture inter-patient variability, all model parameters are patient specific, with a bootstrap particle filter-like Bayesian approach developed to model a set of training data as prior knowledge. We validate our approach against a subset of unseen data, and demonstrate both the predictive ability of our trained model and its limitations.
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http://dx.doi.org/10.1007/s11538-023-01246-0 | DOI Listing |
Clin Cancer Res
September 2025
Amgen (United States), Thousand Oaks, CA, United States.
Purpose: Tarlatamab is a first-in-class, half-life extended bispecific T-cell engager (BiTE®) immunotherapy targeting delta-like ligand 3 (DLL3) currently approved for the treatment of adult patients with small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Here we report tarlatamab exposure-response relationships to inform dose selection in patients with SCLC.
Experimental Design: Pharmacokinetic data were correlated with therapeutic effect [exposure-response (ER) analyses] for efficacy and safety measures using pooled data from DeLLphi-300 and DeLLphi-301 studies.
IEEE Trans Med Imaging
September 2025
Intravoxel Incoherent Motion (IVIM) MRI is a contrast-agent-free microvascular imaging method finding increasing use in biomedicine. However, there is uncertainty in the ability of IVIM-MRI to quantify tissue microvasculature given MRI's limited spatial resolution (mm scale). Nine NRG mice were subcutaneously inoculated with human pancreatic cancer BxPC-3 cells transfected with DsRed, and MR-compatible plastic window chambers were surgically installed in the dorsal skinfold.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
The mutagenic translesion synthesis (TLS) pathway, which is critically dependent on REV1's ability to recruit inserter TLS polymerases and the POLζ extender polymerase, enables cancer cells to bypass DNA lesions while introducing mutations that likely contribute to the development of chemotherapy resistance and secondary malignancies. Targeting this pathway represents a promising therapeutic strategy. Here, we demonstrate that the expression of the C-terminal domain (CTD) of human REV1, a ca.
View Article and Find Full Text PDFAnticancer Drugs
September 2025
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.
Nonsmall cell lung cancer (NSCLC) with SMARCA4 deficiency represents a rare subset of lung tumors characterized by early metastasis, poor response to chemotherapy, and unfavorable prognosis. Established therapy strategies for SMARCA4-deficient NSCLC remain elusive. While immune checkpoint inhibitors have been proposed as a potential solution, their efficacy remains uncertain.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
September 2025
Department of Pharmacology, Acharya & BM Reddy College of Pharmacy, Acharya Dr. Sarvepalli Radhakrishna Road, Achit Nagar (Post), Soldevanahalli, Bengaluru, 560107, India.
This study aimed to synthesize and evaluate the anticancer activity of novel chalcone derivative against colon cancer by in vitro cytotoxicity against HCT-116 (Research Resource Identifiers:CVCL_D4JB) cell line and in vivo using EAC (Research Resource Identifiers: CVCL_1306) and DLA (Research Resource Identifiers: CVCL_VR37) cells inoculated Swiss albino mice. The present study aimed to synthesize the new chalcone derivatives and conduct its anti-colon cancer activity both in vitro and in vivo. The designed compounds were subjected to in silico studies like binding pocket analysis, molecular docking, and ADME studies.
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