Related papers: Cancer risk is not (just) bad luck
Tomasetti and Vogelstein (2015a) find that the incidence of a set of cancer types is correlated with the total number of normal stem cell divisions. Here, we separate the effects of standing stem cell number (i.e., organ or tissue size) and…
There are numerous stochastic models for cancer risk for a given tissue. Many rely on the following two hypotheses. 1. There is a fixed probability that a given cell division will eventually lead to a cancerous cell. 2. Cell divisions are…
This manuscript has been written to address questions related to our recent publication (Science 347:78-81, 2015). We appreciate the many reactions to this paper that have been communicated to us, either privately or publicly. The following…
Although somatic mutations are the main contributor to cancer, underlying germline alterations may increase the risk of cancer, mold the somatic alteration landscape and cooperate with acquired mutations to promote the tumor onset and/or…
Cancer has been characterized as a constellation of hundreds of diseases differing in underlying mutations and depending on cellular environments. Carcinogenesis as a stochastic physical process has been studied for over sixty years, but…
Tomasetti and Vogelstein (2015) collected data on 31 different tissue types and found a correlation of 0.8 between the logarithms of the incidence of cancer (LCI), and the estimated number of stem cell divisions in those tissues (LSCD).…
Mutations can arise from the chance misincorporation of nucleotides during DNA replication or from DNA lesions that are not repaired correctly. We introduce a model that relates the source of mutations to their accumulation with cell…
We propose a one mutation model for cancer with a mutation rate that increases with time. Under rather general hypotheses the number of mutations is necessarily a (non homogeneous) Poisson process with the prescribed mutation rate. We show…
Cancer results from genetic alterations that disturb the normal cooperative behavior of cells. Recent high-throughput genomic studies of cancer cells have shown that the mutational landscape of cancer is complex and that individual cancers…
The biggest Breast cancer is increasingly a major factor in female fatalities, overtaking heart disease. While genetic factors are important in the growth of breast cancer, new research indicates that environmental factors also play a…
Mutation-induced drug resistance in cancer often causes the failure of therapies and cancer recurrence, despite an initial tumor reduction. The timing of such cancer recurrence is governed by a balance between several factors such as…
Tumor recurrence, driven by the evolution of drug resistance is a major barrier to therapeutic success in cancer. Resistance is often caused by genetic alterations such as point mutation, which refers to the modification of a single genomic…
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…
Many common diseases have a complex genetic basis in which large numbers of genetic variations combine with environmental and lifestyle factors to determine risk. However, quantifying such polygenic effects and their relationship to disease…
The diversity of cell populations is regulated by extracellular and intracellular variability. The latter includes genetic, epigenetic and stochastic variability, all contributing to the experimentally observed heterogeneity in response to…
Although the survival rate of cancer patients has significantly increased due to advances in anti-cancer therapeutics, one of the major side effects of these therapies, particularly radiotherapy, is the potential manifestation of…
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.…
Development of a tumor is known to be a result of accumulation of DNA changes in somatic cells. However, the processes of how DNA changes are produced and how they accumulate in somatic cells are not clear. DNA changes include two types:…
The transition from a normal to cancerous cell requires a number of highly specific mutations that affect cell cycle regulation, apoptosis, differentiation, and many other cell functions. One hallmark of cancerous genomes is genomic…
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…