Evolutionary foundations for cancer biology

Aktipis, C. Athena; Nesse, Randolph M.

doi:10.1111/eva.12034

Cited by 184 publications

(168 citation statements)

References 134 publications

(225 reference statements)

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“…Our study applies a detailed molecular framework to view cancer as a failure of the systems supporting increased organismal complexity (31,32). This is an important step toward understanding how macroevolutionary processes left vulnerabilities that lead to cancer and how they may be exploited in practical terms to improve treatment outcomes, facilitating the application of "Darwinian medicine" to oncology (33).…”

Section: Discussionmentioning

confidence: 99%

Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors

Trigos

Pearson

Papenfuss

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

181

217

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Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained proliferation, suppression of cell death, and altered metabolism. These phenotypic commonalities have been proposed to stem from disruption of conserved regulatory mechanisms evolved during the transition to multicellularity to control fundamental cellular processes such as growth and replication. Dating the evolutionary emergence of human genes through phylostratigraphy uncovered close association between gene age and expression level in RNA sequencing data from The Cancer Genome Atlas for seven solid cancers. Genes conserved with unicellular organisms were strongly up-regulated, whereas genes of metazoan origin were primarily inactivated. These patterns were most consistent for processes known to be important in cancer, implicating both selection and active regulation during malignant transformation. The coordinated expression of strongly interacting multicellularity and unicellularity processes was lost in tumors. This separation of unicellular and multicellular functions appeared to be mediated by 12 highly connected genes, marking them as important general drivers of tumorigenesis. Our findings suggest common principles closely tied to the evolutionary history of genes underlie convergent changes at the cellular process level across a range of solid cancers. We propose altered activity of genes at the interfaces between multicellular and unicellular regions of human gene regulatory networks activate primitive transcriptional programs, driving common hallmark features of cancer. Manipulation of cross-talk between biological processes of different evolutionary origins may thus present powerful and broadly applicable treatment strategies for cancer.

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Section: Discussionmentioning

confidence: 99%

Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors

Trigos

Pearson

Papenfuss

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

181

217

View full text Add to dashboard Cite

show abstract

“…One of the major problems in the management of cancer is the nonhomogeneous characteristics of cancer cells within a tumor (26). This presents the problem that for a given tumor, some cells will be sensitive to a drug or combination of drugs while others will be resistant with all the variations between these two possibilities.…”

Section: Discussionmentioning

confidence: 99%

Study of gemcitabine‐sensitive/resistant cancer cells by cell cloning and synchrotron FTIR microspectroscopy

et al. 2014

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Over the last few years, significant scientific insight on the effects of chemotherapy drugs at cellular level using synchrotron-based FTIR (S-FTIR) microspectroscopy has been obtained. The work carried out so far has identified spectral differences in cancer cells before and after the addition of drugs. However, this had to account for the following issues. First, chemotherapy agents cause both chemical and morphological changes in cells, the latter being responsible for changes in the spectral profile not correlated with biochemical characteristics. Second, as the work has been carried out in mixed populations of cells (resistant and sensitive), it is important to distinguish the spectral differences which are due to sensitivity/resistance to those due to cell morphology and/or cell mixture. Here, we successfully cloned resistant and sensitive lung cancer cells to a chemotherapy drug. This allowed us to study a more uniform population and, more important, allowed us to study sensitive and resistant cells prior to the addition of the drug with S-FTIR microscopy. Principal component analysis (PCA) did not detect major differences in resistant cells prior to and after adding the drug. However, PCA separated sensitive cells prior to and after the addition of the drug. This would indicate that the spectral differences between cells prior to and after adding a drug might reside on those more or less sensitive cells that have been able to remain alive when they were collected to be studied with S-FTIR microspectroscopy. This is a proof of concept and a feasibility study showing a methodology that opens a new way to identify the effects of drugs on more homogeneous cell populations using vibrational spectroscopy. V C 2014 International Society for Advancement of Cytometry

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“…Another potential example involves benefits provided to cancer stem cells from clonally related, partially differentiated cells (cancer cell 'helpers at the nest', as it were) [68]; this process has been demonstrated in simulations [69], and may be of considerable significance for cancer cell behaviour and evolution.…”

Section: Six Principles Of Hamiltonian Medicinementioning

confidence: 99%

First principles of Hamiltonian medicine

Crespi

Foster

2014

Phil. Trans. R. Soc. B

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We introduce the field of Hamiltonian medicine, which centres on the roles of genetic relatedness in human health and disease. Hamiltonian medicine represents the application of basic social-evolution theory, for interactions involving kinship, to core issues in medicine such as pathogens, cancer, optimal growth and mental illness. It encompasses three domains, which involve conflict and cooperation between: (i) microbes or cancer cells, within humans, (ii) genes expressed in humans, (iii) human individuals. A set of six core principles, based on these domains and their interfaces, serves to conceptually organize the field, and contextualize illustrative examples. The primary usefulness of Hamiltonian medicine is that, like Darwinian medicine more generally, it provides novel insights into what data will be productive to collect, to address important clinical and public health problems. Our synthesis of this nascent field is intended predominantly for evolutionary and behavioural biologists who aspire to address questions directly relevant to human health and disease.

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Evolutionary foundations for cancer biology

Cited by 184 publications

References 134 publications

Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors

Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors

Study of gemcitabine‐sensitive/resistant cancer cells by cell cloning and synchrotron FTIR microspectroscopy

First principles of Hamiltonian medicine

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