Elsevier

Seminars in Cancer Biology

Volume 53, December 2018, Pages 42-47
Seminars in Cancer Biology

Review
Explaining the dynamics of tumor aggressiveness: At the crossroads between biology, artificial intelligence and complex systems

https://doi.org/10.1016/j.semcancer.2018.07.003Get rights and content

Abstract

Facing metastasis is the most pressing challenge of cancer research. In this review, we discuss recent advances in understanding phenotypic plasticity of cancer cells, highlighting the kinetics of cancer stem cell and the role of the epithelial mesenchymal transition for metastasis. It appears that the tumor micro-environment plays a crucial role in triggering phenotypic transitions, as we illustrate discussing the challenges posed by macrophages and cancer associated fibroblasts. To disentangle the complexity of environmentally induced phenotypic transitions, there is a growing need for novel advanced algorithms as those proposed in our recent work combining single cell data analysis and numerical simulations of gene regulatory networks. We conclude discussing recent developments in artificial intelligence and its applications to personalized cancer treatment.

Section snippets

Cancer stem cells, phenotypic switching and metastasis

Cancer stem cells (CSCs) have been defined as cells with the capability of self-renewing, generating an heterogeneous population within the tumor [1]. According to this view, tumors expand in a hierarchical way, with CSC at the apex of the tree. The other model of tumor growth is the stochastic one, postulating that cancer cells are heterogeneous but are all able to sustain tumor growth [2]. There was evidence in support of both hypotheses, but according to the recent literature the two models

Plasticity in cancer cells: the epithelial mesenchymal transition

The EMT, controlled by a numbers of transcription factors [19], is associated with the loss of cell-cell adhesion and the gain of invasive traits and is therefore a hallmark of plasticity within a stem cell population and appears particularly relevant for tumors. Almost 80% of human malignancies which origin from epithelial tissues express mesenchymal markers, being usually associated with a more aggressive phenotype [19], [20], [21], [22]. More recently, interesting evidence shows that the EMT

Cancer niche: new challenges

Tumor cells require nutrients and signals from the surrounding microenvironment which also regulates a dynamic balance between CSCs and CCs. The tumor niche comprises different types of cells in addition to a non-cellular component (cytokines, growth factors, etc.), mainly cancer-associated fibroblasts (CAF) and macrophages. Macrophages are present in the tumor microenvironment together with immune cells, endothelial cells, fibroblasts and mesenchymal stromal/stem cells and communicate with the

Artificial intelligence, personalized medicine and real world data

Two great revolutions happened in recent years: the possibility to store a great amount of data and the growing speed of computers which are able to perform more operations in a shorter time. These two simple technological improvements are already able to speed up many human daily functions and also have an impact on medicine, including cancer. Computer algorithms and data analysis tools are behind several consumer services from travel agencies to recommendation systems for books, movies and

Conclusions: precision medicine and tumor plasticity

The idea that tumors are highly heterogeneous is already mainstream in the field of cancer biology. The plasticity of tumor cells driven by the microenvironment, that under the right conditions induces cells to switch and seed new metastasis, is becoming an additional hallmark of cancer. Disentangling the evolution of single cells inside the tumor opens a new interesting area to understand better the complex relationship between tumor cells and the environment. Our new understanding of tumor

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