Revolutionary biology: Evolutionary biology and ecology of cancer summer school supports a growing field

This past week in Cambridge, UK, a new generation of evolutionary biologists gathered to build skills and knowledge to tackle one of the most challenging problems humankind has ever encountered: cancer. The first ever Evolutionary Biology and Ecology of Cancer (EBEC) Summer School at the Wellcome Genome Campus brought together the leading researchers in the emerging field of evolution and cancer to teach the next generation of interdisciplinary cancer scientists. In the last several decades, evolutionary and ecological approaches to cancer have grown dramatically, as evidenced by a boom in publications on the topic, new scientific conferences, a new society, and centers for evolution and cancer popping up around the world.The EBEC summer school, supported by the Wellcome Trust, and held in collaboration with the International Society for Evolution, Ecology and Cancer, represents a new phase of the evolution revolution in cancer biology. This new summer school offered trainees in evolutionary biology, ecology, cancer biology, oncology and computational biology an opportunity to learn directly from the leaders of this emerging field and build interdisciplinary connections and collaborations that empower them to use evolution and ecology to understand, prevent and treat cancer.For images and events from the conference, see hereFor a previous TVOL interview with Athena Aktipis, see hereThe evolution revolution began quietly in cancer biology. In 1976, cancer biologist Peter Nowell published a paper describing cancer as evolutionary problem. For decades the field lay relatively fallow, and by the time evolutionary biologists began to discover cancer as an evolutionary phenomenon in the 1990s, there were still only a handful of papers on the topic despite the fact that cancer is fundamentally an evolutionary (and ecological) process. Now the papers on evolution and cancer number in the thousands, and two recent special issues on the topic highlight many aspects of the evolutionary approach to cancer, including an open access special issue in the journal Evolutionary Applications. The topic of comparative oncology – how cancer manifests across life forms and how evolution can help us understand it – is the topic of another special issue, this one in Philosophical Transactions of the Royal Society B, including many open access papers as well.Cells in the body evolve in response to the conditions in our bodies, including the resources being delivered by blood vessels, the predation of the immune system, and even the selective pressures imposed by toxic therapies. And our bodies have evolved to effectively suppress cancer by detecting and eliminating precancerous cells that essentially ‘cheat’ the cooperative systems that enable multicellularity. The interplay between these two levels (among cells in the body and among organisms suppressing cancer) means that cancer is not just an evolutionary problem, but also fundamentally a multilevel selection problem. The opportunities for applying formal tools from evolutionary biology and ecology to cancer are vast, a fact that was recognized by pioneers in the field of evolution and cancer, many of whom came together in at the Wellcome Genome Campus to teach at the EBEC summer school. And if this summer school is any indication, this initially very quiet evolution revolution in cancer biology is starting to get rowdy.The open science policy of the EBEC summer school blew up the Twittersphere with hundreds of tweets per day (#EBECancer16), providing a running report to interested students and professors around the world. The promise of the evolutionary and ecological approach for addressing the central challenges of cancer was not missed on Gary An, professor of Surgery at the University of Chicago who tweeted “Why is not the content of #EBECancer16 driving the #CancerMoonshot? Analogy: #evolution 2 #cancer = #physics 2 #rocketscience.”Several hundred tweets from the course including slides, summaries and photos were captured in the Evolutionary Biology and Ecology of Cancer Summer School 2016 Storify. Some of the key points covered were:

• Evolution and ecology provide organizing frameworks to understand and simplify the overwhelming complexity of information about cancer.
• The history of a tumor can be reconstructed by examining the cells from a biopsy and reconstructing the evolutionary tree of how those cells are related.
• Cancer is characterized by cells cheating in the foundations of multicellular cooperation including proliferation inhibition, controlled cell death, resource allocation, division of labor and shared environment maintenance. Cancer suppression mechanisms can be considered the ‘cheater detectors’ of the body.
• Cancer is shaped by selection acting on multiple levels, including cancer cells and organisms, also cell clusters or colonies. New data on heterogeneity among metastases suggests that selection at the cancer cell colony may be one of the reasons for apparent cooperation among cancer cells and the emergence of complex traits that facilitate metastasis.
• Cells in our bodies are evolving every day as we age and part of the challenge of suppressing cancer is suppressing evolution among the cells of our bodies.
• In some cases higher cancer risk is associated with fitness enhancing traits including fertility and reproductive competitiveness. This helps to explain why we have not evolved to completely suppress cancer.
• Many of the basic evolutionary and ecological dynamics of a tumor have not specifically been measured including birth and death rates of cells in tumors. Quantifying these is a priority in order to properly parameterize theoretical and predictive models.
• Tumors evolve within the ecology of their microenvironments. Researchers are now beginning to study nutrient or energy cycling in tumors, ecological niches, limiting resources, and the ecological interactions between cells in those habitats.
• Taking the ‘perspective’ of a cancer cell and applying the adaptationist paradigm (looking for the fit between form and function of cancer cells) can help us ask the right questions about what cancer cells are doing.
• Ecological dispersal theory applies to the evolution of cell movement and invasion and may help to predict metastasis
• Immune predation of cancer cells has many parallels with predator-prey interactions that are beginning to be explored in cancer immunology and hold tremendous promise for helping us understand and model the complexities of immune-cancer interaction.

• Adaptive therapy for cancer aims at tumor control rather than eradication. Continuing research in animal models suggests that it can extend life and improve quality of life by slowing down the evolution of cells in tumors. Clinical trials are currently underway in prostate cancer and so far all patients have survived longer than would be expected with traditional therapy.

Lecturers for this course came from around the world and brought diverse fields to students including evolutionary biology, ecology, cancer biology, computer science, cooperation theory, immunology and more. The field of cancer evolutionary biology and ecology is inherently interdisciplinary, a fact reflected in the dense networks of collaboration among many of the leaders of the field, many of whom took a week out of their busy schedules to teach at the first EBEC summer school. “We are all joined together by a common goal – to better treat and prevent cancer by leveraging evolutionary and ecological theory,” says Associate Professor at the ASU Biodesign Institute, Carlo Maley, one of the members of the scientific program committee for the EBEC summer school and a founder of the field. Training the next generation of evolutionary cancer biologists is another goal that this community shares. “This is a new field and one that is developing rapidly,” says Maley. “Teaching students the fundamental principles and tools of evolution and ecology – and showing them how to apply them to cancer - is the best investment we can make in the future of our collective capacity to meet the challenges of cancer. We can approach cancer with the best tools and the best minds wielding them.”During the EBEC summer school, students attended lectures each morning and afternoon, also meeting in small focus groups around shared interests including tumor heterogeneity, the evolution of metastasis, evolutionary drug development and more. The collaborative and interactive culture of the evolution and cancer community rapidly became apparent to students including Soulafa Mamlouk, a postdoctoral fellow at Charite Hospital in Berlin, “Everyone here is friendly and open to different points of view.” This sentiment was echoed by many other students including Karolina Nowakowska, a PhD student at the Institute for Cancer Research in London, who commented that both lecturers and students were “very open to sharing ideas and techniques.” EBEC lecturer Karen Anderson, a breast cancer translational researcher at Mayo and Associate Professor at the Biodesign Institute at Arizona State University agreed with the student participants about the value of the interdisciplinary and open nature of summer school, “The exciting part of this course for me has been getting to communicate with each other about how to understand and measure cancer dynamics.”Through the lectures and informal interactions, students learned principles to apply to their on-going work or found inspiration in new research ideas. “This course has helped me shape the questions I want to work on during my PhD,” said Amro Safadi from the University of Manchester. Students had the opportunity to learn from one another as well, according to Weini Huang, a theoretician at Barts Cancer Institute, “Participating in the focus group helped me to form the right questions that I can now address through modeling.” Other students saw the benefits of the course as more long-term. “Now I have a lot to think about,” said Luka Opasic, a PhD student from the Max Planck Institute for Evolutionary Biology, “and I really want to stay involved in the evolution and cancer community after being a part of this course.” The Wellcome Genome Campus offered accommodations, meals, and even an on-site pub, providing many opportunities for informal interactions among the participants in addition to the lectures and focus group meetings.During student focus group meetings, faculty participated in the first consensus meeting to develop clinical standards for measuring the evolutionary and ecological features of tumors. The result was the establishment of an Evolvability Index for tumors, capturing diversity, change in the tumor over time, and the ecological conditions of the tumor. These guidelines for measuring the evolutionary properties of tumors will be published and made available to researchers and clinicians. “Creating this Evolvability Index is a big step towards standardizing how we measure and evolution in tumors and it will help bring evolution into the clinic,” says Darryl Shibata, a Pathologist at the University of California Keck School of Medicine, who has spearheaded this and other efforts to translate evolution and cancer into clinical practice.The EBEC summer school was supported by the Wellcome Trust and The Kay Kendall Leukaemia Fund and organized in collaboration with the Centre for Evolution and Cancer at the Institute of Cancer Research in London and the International Society for Evolution, Ecology and Cancer. Plans are underway to offer this summer school on an ongoing Biannual basis at the Wellcome Genome Campus, with the next EBEC summer school in Summer of 2018. Other opportunities to learn more about evolutionary and ecological approaches to cancer can be found on the webpage of the International Society for Evolution, Ecology and Cancer (www.iseec.org). In Fall 2017, the next conference of the International Society for Evolution, Ecology and Cancer will be held at the Biodesign Institute at Arizona State University.The excitement about the potential of this field was palpable among EBEC students and faculty alike. “The greatest inspiration is seeing these young, smart students ready to weave together all the threads of evolution, ecology, computational modeling and cancer biology to make progress on the complex problem of cancer,” said Joel Brown, an EBEC lecturer and Ecologist at the University of Illinois at Chicago. “It makes me truly optimistic to see the shift in thinking happening here as we come together from so many different disciplines. It’s clear we all appreciate each other, but more than that, we need each other to really understand what’s going on in cancer.”