Frank Laukien - Overview and Purpose of the Cancer & Evolution Symposium

Good morning everybody, or whatever your time zone may be. Good morning to those of you on the East Coast, and a very early good morning from our many participants from the West Coast. A little bit more civilized timing for Europe, and I know we have some participants from Japan, Australia, New Zealand, Singapore, and other places. Welcome to the Cancer and Evolution Symposium, which was supposed to be here in Boston, Massachusetts, but due to COVID it is all online. I do assure you, however, that we have absolutely beautiful foliage as I drove to work this morning; it is stunning this year. Take my word for it for now. My name is Frank Laukien. I have a number of interests and relationships to evolution and cancer. I'm the author of a manuscript on a book called Natural Evolution 4.0 about feedback-driven and actively accelerated organismal biological evolution that also touches upon cancer. I've also had the honor of working on the Archology Think Tank with Azra Raza, and then the Harvard Origins of Life initiative with Dimitar Sasselov. I'm also the CEO of Bruker Corporation, but this event is not related to the corporation in any way. I'd like to welcome you on behalf of my co-moderator Jeff Townsend, who will be moderating the second half of today and also co-moderate the panel discussion with me today. Jeff is online; he of course at the Yale School of Public Health did a similar workshop about a year ago. Thanks for moderating the first day with me. I'd like to thank the co-organizers, many of whom will be speaking today or tomorrow, and of course I'd like to thank all of the speakers and the advisory committee for putting together an absolutely outstanding program for this Cancer and Evolution Symposium. I'm going to start with a question—not to check whether everybody's awake, but just to get going. I'm not looking for verbal answers right now, but perhaps you can use the chat function. That's also how you will submit questions for the speakers during the day, which the moderators will pass on. I was wondering whether we might have a consensus among the speakers, or perhaps also the participants, on two very basic statements: namely, that the insight that cancer is inherently a real-time evolutionary or quasi-evolutionary phenomenon has not yet entered the mainstream of oncology—do you agree or disagree with that statement? And then the second statement: would you agree that cancers are fundamentally characterized by the parallel evolution of heterogeneous multiclonal cancer cell quasi-species, interacting with the dynamic host tumor microenvironment and immune system? I'd like to remind all of us that the reason we're really here is to contribute to progress—not only conceptual and research progress, but hopefully over time and indirectly at least—to sustainable, meaningful, and major improvements in progression-free survival and outcomes for individual cancer patients, but also perhaps begin to reduce and mitigate preventable cancer risks and cancer incidence at a population health level. A little bit on organization and logistics: please adhere to the schedule and your speaking time slot very precisely, literally to the second. This is essential for an online symposium. Any questions, please submit them via the Zoom chat, which will be addressed by moderators and speakers as time permits. The symposium will be recorded; all talks will be posted to a YouTube channel at the end of each day, where they can be accessed via our cancerevolution.org website. If you do not wish for your talk to be posted, please let us know—send an email to Diane. We are encouraging speakers and participants to be actively engaged for all three half-days, simply because we think the interactions during the talks and panel discussions will make this symposium much more than the sum of presentations. We will all strive for constructive debate, even where we have different scientific opinions. We will try to reach consensus where possible in order to gain insights into how to prioritize cancer research, prevention, early screening, diagnostics, risk stratification, and crucially for therapy improvements where possible. Finally, I'd like to point out that in the two-week period after the symposium—the last two weeks of October—selected speakers have scheduled voluntary Q&A sessions for interested participants. All times and login details are available on our C&E symposium website. We will publish graphical reviews of the symposium and panel discussions in a special issue of Progress of Biophysics and Molecular Biology; the submission deadline is November 30th. Graphical reviews are extended abstracts with explanatory figures, so if you've submitted a presentation, you should be almost done. Co-editor-in-chief Denis Noble has invited Paul Davies, Henry Heng, Ken Pienta, and Jim Shapiro as guest editors. We also plan to submit a scientific summary as a perspective article, and a clinical impact report as a clinical perspective article. Ken Pienta and Bill O'Day have agreed to put this together at the end of the symposium for a respected medical journal. A number of people from the scientific press wanted to attend but could not spare three half-days, so we will issue a post-symposium scientific press release to interested science and medicine journalists and writers. This symposium comes at the right time; it could mark an inflection point on how cancer and evolution are viewed together, with far-reaching ramifications for oncology as a research and clinical field, and most importantly for cancer patients. It remains to be seen whether this Cancer and Evolution Symposium culminates in a lecture series and discussion forum that we may continue on a monthly basis. There is discussion of a second symposium—hopefully in person, if we are all vaccinated by then—for the fall of 2021. We may form either a new Cancer and Evolution Society or evolve into a Cancer and Evolution Interest Group with a satellite meeting at a larger cancer meeting or scientific conference. To give a preview of the scientific and medical topics: we want to improve our understanding and exchange views on how cancer cell evolution truly works—at the genetic, epigenetic, and DNA genome level, distinguishing it from the RNA living genome that some of you will refer to. Giants in the field like Bob Weinberg and others who laid the foundation for somatic mutation theory will discuss founder, driver, and passenger mutations in oncogenes and tumor suppressors. We will also hear about much more dramatic DNA insertions and rewrites via reverse transcription, viral or exosome vectors for major alterations in gene and DNA regulation, as seen in recent early detection studies. Among cancer cells, as they proliferate, there is essentially heritable epigenetics—for instance, methylation markers. We'll look at major genome destabilizations, which Henry Heng refers to as genome chaos, and large-scale genome reorganizations via kataegis, localized hypermutation, or chromothripsis—cluster chromosomal rearrangements. Finally, as Ting Wu and George Church have pointed out in recent papers, the genome is certainly a 3D functional entity, not just a linear array of genes and gene regulatory sites. All of that needs to be taken into consideration. Henry Heng and others will stress that karyotype changes are frequent, and aneuploidy, polyploidy, and even multinucleated cells—as Ken Pienta and others will show—play a major role in cancer. But it's also important to look at gene expression and phenotype inheritance of these successive cancer cell generations. We'll look at transcriptomics, proteomics, post-translational modifications. On Friday, I'll talk about the glycomic and sugar coat, heritable surface neoantigens, etc. A fascinating contribution from Scott Bonner and others on extracellular vehicles and exosomes' role in invasiveness and metastasis. I want to introduce Azra in a moment, but let me just finish on this slide. It will also be important to look at the co-evolution—or perhaps development—of the host response and how cancer modulates or suppresses the immune system. Many aspects play into that, including looking at the malignancy-enabling stroma and extracellular matrix. So cancer biology is extremely complex; it's not only the cancer cells themselves but also the host and its various proteomic, protein-protein interaction, and metabolic biomarkers. Hopefully all of this will give us new insights for early detection and diagnostics—something that Azra is particularly interested in—and we will also be talking about cancer therapy. Bob Gatenby and others will be talking about adaptive and extinction therapy strategies. So it'll be a very exciting symposium. For a couple of slides that I will not speak to but invite you to look up if you're truly interested: what's going on in the history of science and organismal evolution. There is major upheaval in organismal evolution—at least the concepts and the theory are evolving. There are many reasons why the modern synthesis is incomplete, perhaps even inaccurate; these are listed here, and many of the authors that have contributed to the new extended framework of organismal evolution, some of them are present at the symposium, others you can look up on the page that will be posted tonight.