Multiscale modelling of cancer progression and treatment control : the role of intracellular heterogeneities in chemotherapy treatment

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 functional changes at the cellular and tissue scale, creating a heterogenous cancer cell population. Anticancer drugs are effective in controlling cancer growth by inflicting damage to various target molecules and thereby triggering multiple cellular and intracellular pathways, leading to cell death or cell-cycle arrest. One of the major impediments in the chemotherapy treatment of cancer is drug resistance driven by multiple mechanisms, including multi-drug and cell-cycle mediated resistance to chemotherapy drugs. In this article, we discuss two hybrid multiscale modelling approaches, incorporating multiple interactions involved in the sub-cellular, cellular and microenvironmental levels to study the effects of cell-cycle, phase-specific chemotherapy on the growth and progression of cancer cells.PostprintPeer reviewe

Quantitative Predictive Modelling Approaches to Understanding Rheumatoid Arthritis:A Brief Review

Rheumatoid arthritis is a chronic autoimmune disease that is a major public health challenge. The disease is characterised by inflammation of synovial joints and cartilage erosion, which lead to chronic pain, poor life quality and, in some cases, mortality. Understanding the biological mechanisms behind the progression of the disease, as well as developing new methods for quantitative predictions of disease progression in the presence/absence of various therapies is important for the success of therapeutic approaches. The aim of this study is to review various quantitative predictive modelling approaches for understanding rheumatoid arthritis. To this end, we start by briefly discussing the biology of this disease and some current treatment approaches, as well as emphasising some of the open problems in the field. Then, we review various mathematical mechanistic models derived to address some of these open problems. We discuss models that investigate the biological mechanisms behind the progression of the disease, as well as pharmacokinetic and pharmacodynamic models for various drug therapies. Furthermore, we highlight models aimed at optimising the costs of the treatments while taking into consideration the evolution of the disease and potential complications.Publisher PDFPeer reviewe

Mathematical modelling of cancer invasion : a review

Funding: MAJC gratefully acknowledges the support of EPSRC Grant No. EP/S030875/1 (EPSRC SofTMech∧MP Centre-to-Centre Award).A defining feature of cancer is the capability to spread locally into the surrounding tissue, with cancer cells spreading beyond any normal boundaries. Cancer invasion is a complex phenomenon involving many inter-connected processes at different spatial and temporal scales. A key component of invasion is the ability of cancer cells to alter and degrade the extracellular matrix through the secretion of matrix-degrading enzymes. Combined with excessive cell proliferation and cell migration (individual and collective), this facilitates the spread of cancer cells into the local tissue. Along with tumour-induced angiogenesis, invasion is a critical component of metastatic spread, ultimately leading to the formation of secondary tumours in other parts of the host body. In this paper we present an overview of the various mathematical models and different modelling techniques and approaches that have been developed over the past 25 years or so and which focus on various aspects of the invasive process.Postprin

Mathematical Modelling of Cancer Invasion:The Multiple Roles of TGF-β Pathway on Tumour Proliferation and Cell Adhesion

VB acknowledges support from an Engineering and Physical Sciences Research Council (UK) grant number EP/L504932/1. RE was partially supported by an Engineering and Physical Sciences Research Council (UK) grant number EP/K033689/1.In this paper, we develop a non-local mathematical model describing cancer cell invasion and movement as a result of integrin-controlled cell–cell adhesion and cell–matrix adhesion, and transforming growth factor-beta (TGF-β) effect on cell proliferation and adhesion, for two cancer cell populations with different levels of mutation. The model consists of partial integro-differential equations describing the dynamics of two cancer cell populations, coupled with ordinary differential equations describing the extracellular matrix (ECM) degradation and the production and decay of integrins, and with a parabolic PDE governing the evolution of TGF-β concentration. We prove the global existence of weak solutions to the model. We then use our model to explore numerically the role of TGF-β in cell aggregation and movement.Publisher PDFPeer reviewe

Dissipative particle dynamics simulation of critical pore size in a lipid bilayer membrane

C.B. was partially supported by the NSF through grant no. DMS-1148284. M.C. gratefully acknowledges support of EPSRC grant no. EP/N014642/1 (EPSRC Centre for Multiscale Soft Tissue Mechanics–With Application to Heart & Cancer). A.M. was partially supported by the NSF through grant nos. DMS-1521266 and DMS-1552903.We investigate with computer simulations the critical radius of pores in a lipid bilayer membrane. Ilton et al. (Ilton et al. 2016 Phys. Rev. Lett.117, 257801 (doi:10.1103/PhysRevLett.117.257801)) recently showed that nucleated pores in a homopolymer film can increase or decrease in size, depending on whether they are larger or smaller than a critical size which scales linearly with film thickness. Using dissipative particle dynamics, a particle-based simulation method, we investigate the same scenario for a lipid bilayer membrane whose structure is determined by lipid–water interactions. We simulate a perforated membrane in which holes larger than a critical radius grow, while holes smaller than the critical radius close, as in the experiment of Ilton et al. (Ilton et al. 2016 Phys. Rev. Lett.117, 257801 (doi:10.1103/PhysRevLett.117.257801)). By altering key system parameters such as the number of particles per lipid and the periodicity, we also describe scenarios in which pores of any initial size can seal or even remain stable, showing a fundamental difference in the behaviour of lipid membranes from polymer films.Publisher PDFPeer reviewe

Introduction to ‘Making the most of AI’s potential: cross-disciplinary perspectives on the role of AI in science and society’

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