49 research outputs found
Cancer recurrence times from a branching process model
As cancer advances, cells often spread from the primary tumor to other parts
of the body and form metastases. This is the main cause of cancer related
mortality. Here we investigate a conceptually simple model of metastasis
formation where metastatic lesions are initiated at a rate which depends on the
size of the primary tumor. The evolution of each metastasis is described as an
independent branching process. We assume that the primary tumor is resected at
a given size and study the earliest time at which any metastasis reaches a
minimal detectable size. The parameters of our model are estimated
independently for breast, colorectal, headneck, lung and prostate cancers. We
use these estimates to compare predictions from our model with values reported
in clinical literature. For some cancer types, we find a remarkably wide range
of resection sizes such that metastases are very likely to be present, but none
of them are detectable. Our model predicts that only very early resections can
prevent recurrence, and that small delays in the time of surgery can
significantly increase the recurrence probability.Comment: 26 pages, 9 figures, 4 table
Cancer Evolution: A Multifaceted Affair.
UNLABELLED: Cancer cells adapt and survive through the acquisition and selection of molecular modifications. This process defines cancer evolution. Building on a theoretical framework based on heritable genetic changes has provided insights into the mechanisms supporting cancer evolution. However, cancer hallmarks also emerge via heritable nongenetic mechanisms, including epigenetic and chromatin topological changes, and interactions between tumor cells and the tumor microenvironment. Recent findings on tumor evolutionary mechanisms draw a multifaceted picture where heterogeneous forces interact and influence each other while shaping tumor progression. A comprehensive characterization of the cancer evolutionary toolkit is required to improve personalized medicine and biomarker discovery. SIGNIFICANCE: Tumor evolution is fueled by multiple enabling mechanisms. Importantly, genetic instability, epigenetic reprogramming, and interactions with the tumor microenvironment are neither alternative nor independent evolutionary mechanisms. As demonstrated by findings highlighted in this perspective, experimental and theoretical approaches must account for multiple evolutionary mechanisms and their interactions to ultimately understand, predict, and steer tumor evolution