Related papers: Population dynamics of multiple ecDNA types
Predictive modeling of the evolutionary dynamics of cancer is a challenge issue in computational cancer biology. In this paper, we propose a general mathematical model framework for the evolutionary dynamics of cancer with plasticity and…
Most human tumors result from the accumulation of multiple genetic and epigenetic alterations in a single cell. Mutations that confer a fitness advantage to the cell are known as driver mutations and are causally related to tumorigenesis.…
In order to analyze data from cancer genome sequencing projects, we need to be able to distinguish causative, or "driver," mutations from "passenger" mutations that have no selective effect. Toward this end, we prove results concerning the…
Cancer progression involves the sequential accumulation of genetic alterations that cumulatively shape the tumour phenotype. In prostate cancer, tumours can follow divergent evolutionary trajectories that lead to distinct subtypes, but the…
A tumor can be thought of as an ecosystem, which critically means that we cannot just consider it as a collection of mutated cells but more as a complex system of many interacting cellular and microenvironmental elements. At its simplest, a…
The unwelcome evolution of malignancy during cancer progression emerges through a selection process in a complex heterogeneous population structure. In the present work, we investigate evolutionary dynamics in a phenotypically heterogeneous…
We study a simple model of DNA evolution in a growing population of cells. Each cell contains a nucleotide sequence which randomly mutates at cell division. Cells divide according to a branching process. Following typical parameter values…
Cells often exhibit different and stable phenotypes from the same DNA sequence. Robustness and plasticity of such cellular states are controlled by diverse transcriptional and epigenetic mechanisms, among them the modification of…
Theoretical reasoning suggests that human cancer may result from knocking down the genetic constraints evolved for maintenance of the metazoan multicellularity, which, however, requires a critical test. Using xenograft-based experimental…
The emergence of acquired drug resistance in cancer represents a major barrier to treatment success. While research has traditionally focused on genetic sources of resistance, recent findings suggest that cancer cells can acquire transient…
The emergence of a predominant phenotype within a cell population is often triggered by a rare accumulation of DNA mutations in a single cell. For example, tumors may be initiated by a single cell in which multiple mutations cooperate to…
Recent evidence suggests that nongenetic (epigenetic) mechanisms play an important role at all stages of cancer evolution. In many cancers, these mechanisms have been observed to induce dynamic switching between two or more cell states,…
Eukaryote genomes contain excessively introns, inter-genic and other non-genic sequences that appear to have no vital functional role or phenotype manifestation. Their existence, a long-standing puzzle, is viewed from the principle of…
Evolution has fascinated quantitative and physical scientists for decades: how can the random process of mutation, recombination, and duplication of genetic information generate the diversity of life? What determines the rate of evolution?…
An endogenous molecular-cellular network for both normal and abnormal functions is assumed to exist. This endogenous network forms a nonlinear stochastic dynamical system, with many stable attractors in its functional landscape. Normal or…
Phenotypic variation is a hallmark of cellular physiology. Metabolic heterogeneity, in particular, underpins single-cell phenomena such as microbial drug tolerance and growth variability. Much research has focussed on transcriptomic and…
We aim to understand the evolution of the genetic composition of cancer cell populations. To achieve this, we consider an individual-based model representing a cell population where cells divide, die and mutate along the edges of a finite…
We investigate the dynamics of cancer initiation in a mathematical model with one driver mutation and several passenger mutations. Our analysis is based on a multi type branching process: We model individual cells which can either divide or…
Extrachromosomal DNA (ecDNA) represents one of the most pressing challenges in cancer biology: circular DNA structures that amplify oncogenes, evade targeted therapies, and drive tumor evolution in ~30% of aggressive cancers. Despite its…
Epigenetics is a driving force of important and ubiquitous phenomena in nature such as cell differentiation or even metamorphosis. Oppositely to its widespread role, understanding the biophysical principles that allow epigenetics to control…