{"id":179603,"date":"2020-07-28T09:54:31","date_gmt":"2020-07-28T13:54:31","guid":{"rendered":"https:\/\/cals.ncsu.edu\/news\/applying-insights-from-ecology-and-evolutionary-biology-to-the-management-of-cancer-an-interview-with-athena-aktipis\/"},"modified":"2024-08-24T03:21:45","modified_gmt":"2024-08-24T07:21:45","slug":"applying-insights-from-ecology-and-evolutionary-biology-to-the-management-of-cancer-an-interview-with-athena-aktipis","status":"publish","type":"post","link":"https:\/\/cals.ncsu.edu\/news\/applying-insights-from-ecology-and-evolutionary-biology-to-the-management-of-cancer-an-interview-with-athena-aktipis\/","title":{"rendered":"Applying Insights from Ecology and Evolutionary Biology to the Management of Cancer"},"content":{"rendered":"

\"\"Athena Aktipis<\/a> is an Assistant Professor in the Psychology Department at Arizona State University, co-Director of the Human Generosity Project and Director of Human and Social Evolution and co-founder of the Center for Evolution and Cancer at the University of California, San Francisco. Athena\u2019s latest book, <\/span>The Cheating Cell: How Evolution Helps Us Understand and Treat Cancer<\/span><\/i><\/a>, goes back millions of years to examine the many ways that multicellular life-forms\u2014from sponges and cacti to dogs and elephants\u2014have evolved to keep \u201ccheating\u201d cancer cells under control. It then goes on to consider the ways in which we can improve the ways in which we treat and manage cancer based on evolutionary insights. <\/span>Rob Dunn<\/span><\/a> (<\/span>RRD<\/b>) sat down to interview Athena (<\/span>AA<\/b>) about cancer, her book, and the future.\u00a0<\/span><\/p>\n

RRD: <\/b>In ordinary evolutionary biology, two key components are genetic variation and selection. Different organisms of a species differ in their genes. Selection favors some sets of genes relative to others. Do all cancers have genetic variation? Do all cancer cells have to deal with selection?<\/span><\/h3>\n

AA:<\/b> Cancer cells evolve just like any population of individuals evolve. Tumors are made of cancer cells that have many different characteristics (some genetically based, some <\/span>epigenetically<\/b> based) and some of those cells survive and divide better than others do. This means that natural selection happens within tumors, favoring the cancer cells that are best at surviving and replicating.<\/span><\/p>\n

RRD:<\/b> Which kinds of cancers are most useful to think about from an evolutionary perspective?<\/span><\/h3>\n

AA: <\/b>All cancers, really. Cancer is fundamentally an evolutionary process, and so evolution can help us understand how tumors change over time and why some tumors are easier to treat than others.\u00a0<\/span><\/p>\n

RRD:<\/b> What sorts of things tend to favor cancer cells that are resistant to chemotherapy? What are the big factors?<\/span><\/h3>\n

AA:<\/b> There are a lot of different ways for cancer cells to become resistant to chemotherapy. One big one is for them to <\/span>upregulate<\/b> what are called e-flux pumps. These are essentially little pumps on the outside of the cell that let them pump out toxins (like the chemicals used in chemotherapy) from inside the cell, making it easier for them to survive high doses of chemotherapy. Unfortunately the very process of treating a tumor often leads to selection for cells that are resistant to therapy, because cells without these mechanisms of resistance (like e-flux pumps) die, leaving only the resistant cells behind.\u00a0<\/span><\/p>\n

RRD: <\/b>So in these cases chemotherapy inadvertently favors the subset of cells able to spit the chemotherapy drugs back out. They are the ones left and they then beget the next generation that, because it has the same genes, is also able to spit the drugs out? Is that more or less right?<\/span><\/h3>\n

AA: <\/b>Yes, exactly. The cancer cells that can survive therapy give rise to the next generation of cells in the tumor, and they pass along the genes that code for that resistance. But often resistance is also a matter of epigenetics – the gene expression state that the cell is in. And that epigenetic state can also get passed along when cells divide.\u00a0\u00a0<\/span><\/p>\n

RRD: <\/b>But sorry, you were saying\u2026\u00a0<\/span><\/h3>\n

AA: <\/b>When we take this problem of the evolution of resistance really seriously, it can point us in the direction of new approaches to treatment. Some of the most exciting work going on in evolution and cancer is a new kind of therapy called \u2018<\/span>Adaptive Therapy<\/span><\/a>,\u2019 which aims to control the tumor rather than eradicate it. With this new approach, low doses of chemotherapy are used only when the tumor is growing, which doesn\u2019t select for resistance and makes it possible to keep using the same drug to treat the tumor for a very long time.\u00a0<\/span><\/p>\n

RRD: <\/b>Why does only using the chemotherapy when the tumor is growing prevent resistance from evolving?<\/span><\/h3>\n

AA: <\/b>The standard approach of high dose selects for resistance because it only leaves behind cells that can survive in the presence of the drug. By treating the tumor only when it is growing, adaptive therapy keeps the tumor under control without eliminating all the sensitive cells – sensitive cells are those cells that die in the presence of the chemotherapy. Keeping sensitive cells around is the key to making it possible to keep the tumor under control in the long term. When you aren\u2019t applying therapy the tumor grows, but generally the sensitive cells grow faster than the resistant cells (because resistance is usually metabolically costly for cells so it slows them down). So as long as there are sensitive cells around, treatment can keep working for a long time.That\u2019s the basic principle behind adaptive therapy.<\/span><\/p>\n

RRD:<\/b> What sorts of things tend to favor cancers that are metastatic and spread through the body?<\/span><\/h3>\n

AA:<\/b> Metastasis<\/b> is one of the biggest mysteries in cancer biology. There is no gene responsible for it, no molecular pathway to target; it is really hard to figure out why metastasis happens in the first place. Evolution and ecology can help, though.\u00a0<\/span><\/p>\n

RRD: <\/b>How?<\/span><\/h3>\n

AA:<\/b> Well, we know, for example, that in many species that when they begin to use up their resources they often disperse. This is the same in a tumor where the high metabolism of cancer cells leads them to deplete the local resources around them, favoring <\/span>cells that can move<\/span><\/a>, invade and look for more resources. Cooperation among cancer cells also probably helps them to <\/span>survive the challenging process of metastasizing<\/span><\/a>. I think this is one of the most exciting areas of work in cancer biology, because if we can figure out how cancer cells are cooperating during metastasis, we can try to interfere with that cooperation to prevent or treat metastatic cancer.<\/span><\/p>\n

RRD: <\/b>Do you think of cancers as being part of the body or as something foreign to it?<\/span><\/h3>\n

AA:<\/strong> All multicellular organisms are susceptible to cancer, because <\/span>cells in our body can evolve to cheat<\/span><\/a> – to take advantage of the cooperation that all of our cells are usually engaged in to make us viable. This means that our susceptibility to cancer is a fundamental part of being a multicellular life form. Cancer arises from the cells of our own body, but then it takes on new characteristics as it evolves. So it is something dangerous that comes from a mutated version of ourselves.\u00a0<\/span><\/p>\n

RRD: <\/b>Can you trace the evolutionary history of cancer cells in a body? A sort of biblical who begat who within a person?<\/span><\/h3>\n

AA: <\/b>Yes, cancer evolutionary biologists make phylogenetic trees that can show the <\/span>evolutionary history of cancer cells<\/span><\/a> in the body. By taking samples from different places in a tumor and then <\/span>sequencing<\/b> the genomes of many different cells, it is possible to reconstruct the overall \u2018family tree\u2019 of a tumor (and sometimes also the metastases).\u00a0<\/span><\/p>\n

RRD: <\/b>What are the steps, whether it is three or seven or however many, to managing cancer while taking evolutionary theory into account?<\/span><\/h3>\n

AA:<\/b>\u00a0<\/span><\/p>\n