Gibin Powathil

• PhD
• Professor at Swansea University

Epithelial-to-mesenchymal transition (EMT) plays a key role in the progression of cancer tumours and can make treatment significantly less successful for patients. EMT occurs when a cell gains a different phenotype and possesses different behaviours to those previously exhibited. This may result in enhanced drug resistance, higher cell plasticity,...

The interplay between drug-sensitive and drug-resistant cancer cells has been observed to impact cell-to-cell interactions in experimental settings. However, the role that space plays in these interactions remains unclear. In this study, we develop mathematical models to investigate how spatial factors affect cell-to-cell competition between drug-s...

Hypoxia Inducible Factor (HIF), the main actor in the cell response to hypoxia, represents a potential target in cancer therapy. HIF is involved in many biological processes such as cell proliferation, survival, apoptosis, angiogenesis, iron metabolism and glucose metabolism. This protein regulates the expressions of Lactate Dehydrogenase (LDH) and...

The sudden outbreak of the COVID-19 pandemic presented governments, policy makers and health services with an unprecedented challenge of taking real-time decisions that could keep the disease under control with non-pharmaceutical interventions, while at the same time limit as much as possible severe consequences of a very strict lockdown. Mathemati...

The ataxia-telangiectasia and Rad3-related (ATR) inhibitor ceralasertib and the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib have shown synergistic activity, in vitro, in the FaDu ATM-KO cell line. It was found that combining these drugs with lower doses and for shorter treatment periods induced greater or equal toxicity in cancer cells t...

A key feature distinguishing 3D bioprinting from other 3D cell culture techniques is its precise control over created structures. This property allows for the high-resolution fabrication of biomimetic structures with controlled structural and mechanical properties such as porosity, permeability, and stiffness. However, analyzing post-printing cellu...

Oxygenation of tumors and the effect of hypoxia on cancer cell metabolism is a widely studied subject. Hypoxia‐inducible factor (HIF), the main actor in the cell response to hypoxia, represents a potential target in cancer therapy. HIF is involved in many biological processes such as cell proliferation, survival, apoptosis, angiogenesis, iron metab...

Radiotherapy is a commonly used treatment for cancer and is usually given in varying doses. Mathematical modelling of radiation effects traditionally means the modelling or estimation of cell-kill due to its direct exposure to irradiation and sometimes ignoring other multiple direct/indirect effects. However, advances in molecular biology have expa...

We combine a systems pharmacology approach with an agent-based modelling approach to simulate LoVo cells subjected to AZD6738, an ATR (ataxia–telangiectasia-mutated and rad3-related kinase) inhibiting anti-cancer drug that can hinder tumour proliferation by targeting cellular DNA damage responses. The agent-based model used in this study is governe...

Understanding and designing clinical radiation therapy is one of the most important areas of state-of-the-art oncological treatment regimens. Decades of research have gone into developing sophisticated treatment devices and optimization protocols for schedules and dosages. In this paper, we presented a comprehensive computational platform that faci...

Hypoxia-activated prodrugs (HAPs) present a conceptually elegant approach to not only overcome, but better yet, exploit intra-tumoural hypoxia. Despite being successful in vitro and in vivo, HAPs are yet to achieve successful results in clinical settings. It has been hypothesised that this lack of clinical success can, in part, be explained by the...

Objectives: The objective of this paper is to present the results of discussions at a workshop held as part of the International Congress of Radiation Research (Environmental Health stream) in Manchester UK, 2019. The main objective of the workshop was to provide a platform for radioecologists to engage with radiobiologists to address major questio...

Contemporary mathematical models of solid tumours constitute an invaluable complement to traditional cancer research [1]. Accordingly, we have developed an in silico framework (a computational framework), capable of simulating solid tumours under multiple conditions, emulating established clinical scenarios.

Understanding and designing clinical radiation therapy is one of the most important areas of state-of-the-art oncological treatment regimens. Decades of research have gone into developing sophisticated treatment devices and optimization protocols for schedules and dosages. In this paper, we presented a comprehensive computational platform that faci...

Hypoxia-activated prodrugs (HAPs) present a conceptually elegant approach to not only overcome, but better yet, exploit intra-tumoural hypoxia. Despite being successful in vitro and in vivo, HAPs are yet to achieve successful results in clinical settings. It has been hypothesised that this lack of clinical success can, in part, be explained by the...

Multiscale, agent-based mathematical models of biological systems are often associated with model uncertainty and sensitivity to parameter perturbations. Here, three uncertainty and sensitivity analyses methods, that are suitable to use when working with agent-based models, are discussed. These methods are namely Consistency Analysis, Robustness An...

Translating quantitative information between in vitro and in vivo research remains a scientifically and financially challenging step in preclinical drug development processes. However, well-developed in silico tools can be used to facilitate this in vitro to in vivo translation, and we here propose using a data-driven, agent-based model to bridge t...

Tumour hypoxia has been associated with increased resistance to various cancer treatments, particularly radiation therapy. Conversely, tumour hypoxia is a validated and ideal target for guided cancer drug delivery. For this reason, hypoxia-activated prodrugs (HAPs) have been developed, which remain inactive in the body until in the presence of tiss...

Cancers present with high variability across patients and tumors; thus, cancer care, in terms of disease prevention, detection, and control, can highly benefit from a personalized approach. For a comprehensive personalized oncology practice, this personalization should ideally consider data gathered from various information levels, which range from...

In this review we make the statement that hybrid models in oncology are required as a mean for enhanced data integration. In the context of systems oncology, experimental and clinical data need to be at the heart of the models developments from conception to validation to ensure a relevant use of the models in the clinical context. The main applica...

In this opinion paper we make the statement that hybrid models in oncology are required as a mean for enhanced data integration. In the context of systems oncology, experimental and clinical data need to be at the heart of the models developments from conception to validation to ensure a relevant use of the models in the clinical context. The main...

The cellular dispersion and therapeutic control of glioblastoma, the most aggressive type of primary brain cancer, depends critically on the migration patterns after surgery and intracellular responses of the individual cancer cells in response to external biochemical cues in the microenvironment. Recent studies have shown that miR-451 regulates do...

miR-451-AMPK-mTOR system. Development, parameter estimation, analysis, sensitivity analysis, and theoretical implications of the miR-451-AMPK-mTOR core control system. (PDF)

This article presents the results of a workshop held in Stirling, Scotland in June 2018, called to examine critically the effects of low-dose ionising radiation on the ecosphere. The meeting brought together participants from the fields of low- and high-dose radiobiology and those working in radioecology to discuss the effects that low doses of rad...

Supplementary Raw Research Data. This is open data under the CC BY license http://creativecommons.org/licenses/by/4.0/

Tumour recurrence post chemotherapy is an established clinical problem and many cancer types are often observed to be increasingly drug resistant subsequent to chemotherapy treatments. Drug resistance in cancer is a multipart phenomenon which can be derived from several origins and in many cases it has been observed that cancer cells have the abili...

Tumour recurrence post chemotherapy is an established clinical problem and many cancer types are often observed to be increasingly drug resistant subsequent to chemotherapy treatments. Drug resistance in cancer is a multipart phenomenon which can be derived from several origins and in many cases it has been observed that cancer cells have the abili...

If improvements are to be made in tuberculosis (TB) treatment, an increased understanding of disease in the lung is needed. Studies have shown that bacteria in a less metabolically active state, associated with the presence of lipid bodies, are less susceptible to antibiotics, and recent results have highlighted the disparity in concentration of di...

If improvements are to be made in tuberculosis (TB) treatment, an increased understanding of disease in the lung is needed. Studies have shown that bacteria in a less metabolically active state, associated with the presence of lipid bodies, are less susceptible to antibiotics, and recent results have highlighted the disparity in concentration of di...

This consensus paper presents the results of a workshop held in Essen, Germany in September 2017, called to examine critically the current approach to radiological environmental protection. The meeting brought together participants from the field of low dose radiobiology and those working in radioecology. Both groups have a common aim of identifyin...

This consensus paper presents the results of a workshop held in Essen, Germany in September 2017, called to examine critically the current approach to radiological environmental protection. The meeting brought together participants from the field of low dose radiobiology and those working in radioecology. Both groups have a common aim of identifyin...

Combined radiotherapy and hyperthermia offer great potential for the successful treatment of radio-resistant tumours through thermo-radiosensitization. Tumour response heterogeneity, due to intrinsic, or micro-environmentally induced factors, may greatly influence treatment outcome, but is difficult to account for using traditional treatment planni...

Combined radiotherapy and hyperthermia offer great potential for the successful treatment of radio-resistant tumours through thermo-radiosensitization. Tumour response heterogeneity, due to intrinsic, or micro-environmentally induced factors, may greatly influence treatment outcome , but is difficult to account for using traditional treatment plann...

Background A new transcranial focused ultrasound device has been developed that can induce hyperthermia in a large tissue volume. The purpose of this work is to investigate theoretically how glioblastoma multiforme (GBM) can be effectively treated by combining the fast hyperthermia generated by this focused ultrasound device with external beam radi...

Cancer is a complex, multiscale process involving interactions at intracellular, intercellular and tissue scales that are in turn susceptible to microenvironmental changes. Each individual cancer cell within a cancer cell mass is unique, with its own internal cellular pathways and biochemical interactions. These interactions contribute to the funct...

The cellular dispersion and therapeutic control of glioblastoma, the most aggressive type of primary brain cancer, depends critically on the migration patterns after surgery and intracellular responses of the individual cancer cells in response to external biochemical and biomechanical cues in the microenvironment. Recent studies have shown that a...

Cancer is a complex multiscale disease involving inter-related processes across a wide range of temporal and spatial scales. Multiscale mathematical models can help in studying cancer progression and serve as an in silico test base for comparing and optimizing various multi-modality anticancer treatment protocols. Here, we discuss one such hybrid m...

Chemotherapy is one of the most important therapeutic options used to treat human cancers, either alone or in combination with radiation therapy and surgery. Recent studies have indicated that intra-tumoural heterogeneity has a significant role in driving resistance to chemotherapy in many human malignancies. Multiple factors including the internal...

Radiotherapy is a commonly used treatment for cancer and is usually given in varying doses. At low radiation doses relatively few cells die as a direct response to radiation but secondary radiation effects such as DNA mutation or bystander effects affect many cells. Consequently it is at low radiation levels where an understanding of bystander effe...

The multiscale complexity of cancer as a disease necessitates a corresponding multiscale modelling approach to produce truly predictive mathematical models capable of improving existing treatment protocols. To capture all the dynamics of solid tumour growth and its progression, mathematical modellers need to couple biological processes occurring at...

Number of cells when chemotherapy is given after radiation therapy. Two doses of G1 and/or G2 drugs are given at time = 466 h and 496 h, after 5 fractions of radiation therapy (1 week) with a daily dose of 2.5 Gy starting at time = 340 h. (a) Plots when two G1 phase-specific drugs are given after radiation, (b) plots when two G2 phase-specific drug...

Number of cells when a chemotherapy (one dose) is given before and after radiation therapy. Two doses of G1 and/or G2 drugs are given at time = 340 h and 496 h and 5 fractions of radiation therapy (1 week) with a daily dose of 2.5 Gy are given in between the chemotherapy doses, starting at time = 370 h. (a) Plots when two G1 phase-specific drugs ar...

Number of cells when chemotherapy is given during radiation therapy. Two doses of G1 and/or G2 drugs are given at time = 370 h and 400 h, during the 5 fractions of radiation therapy (1 week) with a daily dose of 2.5 Gy starting at time = 340 h. (a) Plots when two G1 phase-specific drugs are given during radiation, (b) plots when two G2 phase-specif...

Plot showing the concentration profile of oxygen supplied from the vasculature. The red coloured spheres represent the blood vessel cross sections and the colour map shows the percentages of oxygen concentration. (TIF)

Percentage of cells in G1 and G2 states with and without radiation. (a) experimental results from [23] and (b) simulation results (percentage of proliferating cells). (TIF)

The spatial distribution of cells within a growing tumour before, during and after the combination therapy. Plots showing the spatial distribution of cells within a growing tumour at (a) time = 340 h, (b) time = 345 h, (c) time = 370 h, (d) time = 420 h, (e) time = 470 h, (f) time = 496 h, (g) time = 500 h and (h) time = 600 h when tumour is treate...

In this paper we use a hybrid multiscale mathematical model that incorporates both individual cell behaviour through the cell-cycle and the effects of the changing microenvironment through oxygen dynamics to study the multiple effects of radiation therapy. The oxygenation status of the cells is considered as one of the important prognostic markers...

s: Thirty-Fifth Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 4‐8, 2012; San Antonio, TX Background: The therapeutic control of cancer progression critically depends on the responses of the individual cells that constitute the entire tumor mass. A key reason for poor therapeutic responses is the emergence of drug resistance due to int...

The therapeutic control of a solid tumour depends critically on the responses of the individual cells that constitute the entire tumour mass. A particular cell's spatial location within the tumour and intracellular interactions, including the evolution of the cell-cycle within each cell, has an impact on their decision to grow and divide. They are...

Tumor oxygenation status is considered one of the important prognostic markers in cancer since it strongly influences the response of cancer cells to various treatments; in particular, to radiation therapy. Thus, a proper and accurate assessment of tumor oxygen distribution before the treatment may highly affect the outcome of the treatment. The he...

Gliomas, the most common primary brain tumors, are diffusive and highly invasive. The standard treatment for brain tumors consists of a combination of surgery, radiation therapy and chemotherapy. Over the past few years, mathematical models have been applied to study untreated and treated brain tumors. In an effort to improve treatment strategies,...