Welcome to Cancer Ecology Commentary

Welcome to Cancer Ecology Commentary, a blog devoted to examining and sharing current research in cancer ecology and cancer evolution. Cancer ecology is the study of malignant neoplasms in conjunction with that malignancy’s accompanying environment and the interactions occurring between them. Cancer evolution is the tendency for cancers to evolve over time in the course of a malignant disease.  

One benefit of viewing cancer from an ecological perspective is the use of the language and ideas from biological ecology as tools to understand and categorize those environmental forces present that influence neoplastic development and evolution. Cancers are dynamic, that is their constituent malignant cell population is subject to change over time. Because cancers are clonal, that is they originate from the neoplastic transformation of a single cell, the process of change which we observe in a cancer over time is often referred to as clonal evolution.

An important hypothesis for cancer ecologists to assess is the belief that just how a cancer evolves reflects that cancer’s response to the character of the host (patient) environment supporting the neoplasm.  The ecologist is interested in defining what the nature of that host environment is which may select certain cancer features acting to enhance the cancer’s chances for successful growth and reproduction in that environment. An important corollary hypothesis considers whether those environmental circumstances are subject to modification to diminish that support for therapeutic influence.

Below are some of the other terms which help describe cancer ecology study:

By ecosystem we mean a biological community, a group of interacting organisms viewed together in their physical environment. A cancer ecosystem then can be thought of as the combination of a neoplasm, comprised of a group of malignant cells and the accompanying environment of the host individual from which the cancer arose and on which it depends for its survival and growth.

A cancer ecologist is someone interested in understanding this interrelationship by characterizing the set of interactions occurring between the cancer and the host. Learning about that dynamic relationship is a way of better understanding the either faciliatory or opposing inhibitory effects of the tumor environment believed to influence tumor behavior.

We can think about that behavior as occurring at multiple levels beginning at the molecular level with the understanding of the cancer genome, the set genetic elements, the genes of a cancer organized into chromosomes. Accompanying the cancer genome is a regulatory system serving to control gene expression, the epigenome. That regulation is accomplished through modifications of DNA-bound proteins allowing control over either more or less gene accessibility. That accessibility, acting as a gate keeper, governs gene expression, the transcription of gene segments of DNA into corresponding messenger RNA often then to be translated into proteins. Genes are subject to mutation - an alteration in the DNA code capable of heightening or suppressing gene function and which may in turn may induce or amplify cancer cell growth. Such mutated genes demonstrating untoward effects on tumor development or growth are often referred to as oncogenes.

A cancer’s particular genome is referred to as its genotype and becomes manifest at the cellular level as the development of an invasive cancer. We define cancer as having occurred once neoplastic cells are found to have crossed over a physical barrier surrounding that organ from which they originated into surrounding tissue, an organ’s stroma. The character of that neoplastic invasion including for example such features as the tumor’s appearance under the microscope, its morphology, or it’s capacity for growth and ability to spread to distant sites, a cancer’s metastasis, or the metabolic pathways which a tumor utilizes to generate energy, a cancer’s metabolism, or a cancer’s ability to evade host anti-cancer immune responses, when taken together can be considered a neoplasm’s phenotype, the observable features of a cancer.

The phenotypic traits of cancer which underpin its development are referred to as the Hallmarks of Cancer. The Hallmarks are those traits seen regularly throughout oncology which act to enhance a neoplasm’s chances for survival, what is termed the neoplasm’s fitness. These traits are examples of adaptive responses by the neoplasm. The existence of tumor adaptations provides strong evidence that neoplasms, like any other organism, follow the laws of evolutionary biology.

In evolution, some traits of an organism improve that organism’s chances for survival in a given environment leading to more organisms bearing that trait. We can say then that trait was selected given its benefit to that organism in fostering improved reproduction. In a similar fashion, Hallmarks, regularly observed tumor traits which characterize a malignancy, are likely to have been selected by some aspect of the host environment providing the cancer with enhanced survival chances.

Given the importance of selection in sculpting the features of a developing neoplasm, the cancer ecologist searches for those host environmental features which may be acting to drive that cancer’s evolution and account for that cancer’s particular pathologic behavior. Some host environmental characteristics may be subject to modification, potentially lessening the influence of that selection-enhanced tumor fitness.  

One important aspect of the cancer’s cellular neighborhood where we can visualize firsthand those host-tumor interactions occurring is referred to as the tumor’s microenvironment. Cell biology has given us tools allowing us to view that neighborhood where neoplastic cells exist in juxtaposition with an accompanying host cellular response. Studies of the tumor microenvironment have provided understanding of the accompanying perturbations in host immunity which neoplasms are known to induce and how neoplasms over time are capable of corrupting anti-tumor host response.

The immune system is represented by dozens of cell subtypes, each identifiable by specific features on their cell surface which in turn are associated with a diverse set of specialized capabilities. By modifying the character of the surrounding host immune response, successfully emerging neoplasms act on the microenvironment to inhibit what ordinarily would be the normal surveillance and anti-tumor response mediated by cellular immunity. However, the means by which that inhibition occurs has come to be better understood and as a consequence led to the availability of immune-modulating therapies, often monoclonal antibodies, now available in the clinic as cancer treatment. These therapeutic antibodies exert their effect through the inhibition of regulatory systems governing immune responsiveness, commonly referred to as immune checkpoint blockade. By alleviating the suppressed state of cellular immunity these antibodies are proving capable of altering the untoward tumor-protective microenvironment acting to resuscitate the cellular anticancer defense and often achieving astonishing responses.

The availability of resources and other conditions found within the tumor microenvironment available to the tumor to exploit can be referred to as the tumor niche. Some neoplasms have the ability to remodel that niche in the process altering that environment to improve chances for tumor survival, a process termed niche construction. For example, some cancers are capable of building a wall around themselves creating their own sanctuary resistant to immune surveillance or response.

In addition to studies of cancer at the molecular or cellular level, cancer ecologists are also interested in examining neoplastic development at the organ level, to consider how organ injury as a consequence of medical illness or toxic environmental exposure may untowardly act to promote neoplasia. Ordinarily the organ systems of an individual function together to maintain homeostasis, the regulation of the organism’s environment to maintain stability in the face of changing environment conditions. Such coordinated actions can be thought of as an example division of labor. From the time of the first multicellular organism, such segregation has provided those organisms with improved efficiency in responding to constantly changing and often deleterious external conditions.

Borrowing ideas from the world of economics we can think of how cells comprising an organ system or organ systems comprising physiology are cooperating with each other to maintain homeostasis. Usually, this cooperation functions normally accounting for the health of that organism. Circumstances though may arise either because of an external stress or alternatively as an internal pathology acting to disincentivize such mutualism. In economics, in a community of individuals, when one individual consumes the benefits of that group but stops contributing to the work of the community we think of that individual as cheating on their fellow community members. Economists use the term ‘tragedy of the commons’ to describe a universal tendency among individuals for such behavior reflecting their goal of self-survival at the expense of community integrity. Similarly, cells within a cooperating organ system may encounter deleterious circumstances such as chronic injury or inflammation within that organ which promote an analogous self-survival response. In cooperation theory a sustained change in this prevailing work/benefit ratio may cause disruption of normal cellular growth control leading to cellular autonomy.

Finally, recalling the highly social nature of human communities, cancer ecologists can begin to describe the untoward human environments and social pathologies that influence human diseases including cancer. A social model of human malignancy allows us to consider how malnutrition, poverty, education, culture, and the distribution of a society’s resources may affect the development of cancer.

Thank you again for visiting Cancer Ecology Commentary. I hope you found this overview useful. Please stop back in the future for new monthly commentary at this site covering aspects related to the above.

James Cunningham