A5038442062- Mathematical Biology Tumor Growth
- Cancer Genomics and Diagnostics
- Gene Regulatory Network Analysis
- Statistical Methods in Clinical Trials
- Computational Drug Discovery Methods
- Prostate Cancer Treatment and Research
- Cancer Research and Treatment
- Radiopharmaceutical Chemistry and Applications
- Science, Research, and Medicine
- Machine Learning in Materials Science
- Machine Learning in Healthcare
- Cancer Cells and Metastasis
- Health Systems, Economic Evaluations, Quality of Life
- Evolution and Genetic Dynamics
- PARP inhibition in cancer therapy
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Medical Imaging Techniques and Applications
- Mental Health Research Topics
- Radiation Effects and Dosimetry
- Nanoplatforms for cancer theranostics
- Prostate Cancer Diagnosis and Treatment
- Nanoparticle-Based Drug Delivery
- Single-cell and spatial transcriptomics
- Microtubule and mitosis dynamics
Weatherford College
2025
Cleveland Clinic
2023-2025
Cleveland Clinic Lerner College of Medicine
2023-2025
Moffitt Cancer Center
2020-2024
University of Oxford
2017-2023
ORCID
2021
University of St Andrews
2016
Adaptive therapy is a dynamic cancer treatment protocol that updates (or ‘adapts’) decisions in anticipation of evolving tumor dynamics. This broad term encompasses many possible protocols patient-specific dose modulation or timing. maintains high levels burden to benefit from the competitive suppression treatment-sensitive subpopulations on treatment-resistant subpopulations. evolution-based approach has been integrated into several ongoing planned clinical trials, including metastatic...
Adaptive therapy aims to tackle cancer drug resistance by leveraging resource competition between drug-sensitive and resistant cells. Here, we present a theoretical study of intra-tumoral during adaptive therapy, investigate under which circumstances it will be superior aggressive treatment.We develop analyse simple, 2-D, on-lattice, agent-based tumour model in cells are classified as fully or resistant. Subsequently, compare this its corresponding non-spatial ordinary differential equation...
Standard-of-care treatment regimens have long been designed for maximal cell killing, yet these strategies often fail when applied to metastatic cancers due the emergence of drug resistance. Adaptive developed as an alternative approach, dynamically adjusting suppress growth treatment-resistant populations and thereby delay, or even prevent, tumor progression. Promising clinical results in prostate cancer indicate potential optimize adaptive protocols. Here, we deep reinforcement learning...
The evolutionary dynamics of tumor initiation remain undetermined, and the interplay between neoplastic cells immune system is hypothesized to be critical in transformation. Colorectal cancer (CRC) presents a unique opportunity study transition malignancy as pre-cancers (adenomas) early-stage cancers are frequently resected. Here, we examine tumor-immune eco-evolutionary from pre-cancer carcinoma using computational model, ecological analysis digital pathology data, neoantigen prediction 62...
Toxicity and emerging drug resistance are important challenges in PARP inhibitor (PARPi) treatment of ovarian cancer. Recent research has shown that evolutionary-inspired algorithms which adapt to the tumor's response (adaptive therapy) can help mitigate both. Here, we present a first step developing an adaptive therapy protocol for PARPi by combining mathematical modelling wet-lab experiments characterize cell population dynamics under different schedules. Using data from vitro Incucyte...
<p>Supplementary Information File</p>
Adaptive therapy (AT) protocols have been introduced to combat drug-resistance in cancer, and are characterized by breaks maximum tolerated dose treatment (the current standard of care most clinical settings). These scheduled maintain tolerably high levels tumor burden, employing competitive suppression treatment-resistant sub-populations treatment-sensitive sub-populations. AT has integrated into several ongoing or planned trials, including metastatic castrate-resistant prostate ovarian...
Standard-of-care cancer therapy regimens are characterized by continuous treatment at the maximum tolerated dose; however, this approach often fails on metastatic cancers due to emergence of drug resistance. An evolution-based paradigm known as 'Adaptive Therapy' has been proposed counter this, dynamically adjusting control, rather than minimize, tumor burden, thus suppressing growth treatment-resistant cell populations and hence delaying patient relapse. Promising clinical results in...
Abstract Osimertinib is a 3rd generation EGFR inhibitor and the newest FDA approved adjuvant therapy for non-small cell lung cancer (NSCLC) with exon 19 deletions or 21 L858R mutation. Although drug can yield impressive initial responses, majority of patients eventually progress due to evolution resistance. While molecular mechanisms underlying resistance have been well studied, little known about ecological evolutionary laws that govern creation subsequent expansion these mutant...
Abstract Tyrosine kinase inhibitors (TKI) have revolutionized treatment of oncogene-driven non-small cell lung cancer (NSCLC). However, almost all patients with advanced disease eventually acquire resistance and the remains largely incurable. Much research is dedicated to identifying targeting molecular mechanisms resistance. But even when challenged by our most treatments, cancers display a remarkable ability adapt. We seek complement development new agents investigating scheduling - dose...
Abstract Standard-of-care cancer therapy regimens are characterized by continual treatment at the maximum tolerated dose, however, this approach often fails on metastatic cancers due to emergence of drug resistance. An evolution-based paradigm known as 'Adaptive Therapy' has been proposed counter this, dynamically adjusting control, rather than minimize, tumor burden, thus suppressing growth treatment-resistant cell populations and hence delaying patient relapse. Promising clinical results...
Avoidance to look others in the eye is a characteristic symptom of Autism Spectrum Disorders (ASD), and it has been hypothesised that quantitative monitoring gaze patterns could be useful objectively evaluate treatments. However, tools measure behaviour on regular basis at manageable cost are missing. In this paper, we investigated whether smartphone-based tool address problem. Specifically, assessed accuracy with which phone-based, state-of-the-art eye-tracking algorithm iTracker can...
Adaptive therapies that alternate between drug applications and drug-free vacations can exploit competition sensitive resistant cells to maximize the time progression. However, optimal dosing schedules depend on properties of metastases, which are often not directly measurable in clinical practice. Here, we proposed a framework for estimating features metastases through tumor response dynamics during first adaptive therapy treatment cycle. Longitudinal prostate-specific antigen (PSA) levels...
Abstract Invasion of healthy tissue is a defining feature malignant tumours. Traditionally, invasion thought to be driven by cells that have acquired all the necessary traits overcome range biological and physical defences employed body. However, in light ever-increasing evidence for geno- phenotypic intra-tumour heterogeneity, an alternative hypothesis presents itself: could collection with distinct together facilitate process? In this paper, we use mathematical model assess feasibility...
Abstract “Control and conquer” - this is the philosophy behind adaptive therapy, which seeks to exploit intra-tumoural competition avoid, or at least, delay emergence of therapy resistance in cancer. Motivated by promising results from theoretical, experimental and, most recently, a clinical study prostate cancer, there an increasing interest extending approach other cancers. As such, it urgent understand characteristics cancer determine whether will respond well not. A plausible candidate...
Abstract (1) Background: Adaptive therapy aims to tackle cancer drug resistance by leveraging intra-tumoral competition between drug-sensitive and resistant cells. Motivated promising results in prostate there is growing interest extending this approach other cancers. Here we present a theoretical study of during adaptive therapy, identify under which circumstances it will be superior aggressive treatment; (2) Methods: We use 2-D, on-lattice, agent-based tumour model examine the impact...
Phylogeny reconstruction with global criteria is NP-complete or NP-hard, hence in general requires a heuristic search. We investigate the powerful, physically inspired, general-purpose simulated annealing, applied to phylogeny reconstruction. Simulated annealing mimics physical process of where liquid gently cooled form crystal. During search, periods elevated specific heat occur, analogous phase transitions. These transitions play crucial role outcome Nevertheless, they have received...
Abstract Immune therapies have shown promise in a number of cancers, and clinical trials using the anti-PD-L1/PD-1 checkpoint inhibitor lung cancer been successful for patients. However, some patients either do not respond to treatment or recurrence after an initial response. It is clear which might fall into these categories what mechanisms are responsible failure. To explore different underlying biological resistance, we created spatially explicit mathematical model with modular framework....
Abstract Integrating mathematical modeling and in vitro experiments to measure ecological interactions cancer Maximilian Strobl, Dagim Tadele, Jeffrey Maltas, Rowan Barker-Clarke, Mina Dinh, Jacob Scott Over the past two decades it has become clear that tumours are complex evolving ecosystems, which different cell populations interact with each other their non-tumour microenvironment. This understanding given rise intriguing idea we might be able leverage these slow, or even revert,...
Abstract Antifragility is a recently coined word used to describe the opposite of fragility. Systems or organisms can be described as antifragile if they derive benefit from systemic variability, volatility, randomness, disorder. Herein, we introduce mathematical framework quantify fragility antifragility cancer cell lines in response treatment variability. This enables straightforward prediction optimal dose schedule for range schedules with identical cumulative dose. We apply this...