June 29, 2021

The Mark Foundation Symposium 2021: Metabolism and Cancer

Becky Bish, PhD

The right connections can catalyze scientific breakthroughs – at Cold Spring Harbor Laboratory, where I was a graduate student, some of the most electrifying moments of inspiration happened in the pub, where, after a long day of scientific presentations, conference attendees would pour in and mingle with the lab’s students and faculty, often with a Mets game on in the background and Tom the bartender doing his part to keep the ideas (and the beers!) flowing. Spontaneous conversations frequently uncovered common threads between seemingly disparate areas of research or led to an epiphany about how to apply a newly developed technique to an unrelated problem. At The Mark Foundation, we’ve made it part of our mission to foster such moments of connection through our intensive workshops, symposia, and other events. And we’ve seen this approach pay off.

Speakers: Lewis Cantley, PhD. Marcia C. Haigis, PhD. Greg M. Delgoffe, PhD.

One of the many negative impacts of the COVID19 pandemic has been the near complete cessation of opportunities for scientists to meet in person and discuss their research. Our last in-person event was our scientific symposium in the early days of March 2020, a thrilling day where over 100 Mark Foundation-funded researchers from all over the world convened to share their exciting results. Over the following months, as it became clear that remote interaction would be the new reality for the near-term future, we thought carefully about how to re-establish opportunities to bring researchers together.

Our solution to sustaining these moments of connection in our temporarily distanced world is the Mark Foundation virtual symposia series. These events focus on an emerging topic in the cancer research community and feature speakers who are leading the way in that area of shared interest.

We held the first Mark Foundation virtual symposium on May 6, 2021 on the topic of Metabolism and Cancer, focusing on the role of metabolic factors in carcinogenesis, tumor progression, and cancer therapy. Nearly a century ago, Otto Warburg and others discovered that even when oxygen is plentiful, cancer cells meet their energy needs not through the metabolic pathways used by normal tissues but through a less efficient process, aerobic glycolysis (fermentation)—a puzzling transformation for cells whose rapid proliferation would seem to demand more, rather than less, energy production. More recently, the study of metabolism in cancer has expanded beyond the focus of metabolic changes in tumor cells themselves, to encompass the impact of metabolic alterations at a systemic level as well as in the local tumor microenvironment.

The research of our three speakers exemplifies this shift in the field. The symposium kicked off with a talk from Lewis Cantley, PhD of Weill Cornell Medicine, who presented his findings that a high glycemic diet, and the insulin resistance that can result from such a diet, can dampen the effects of a novel class of anti-cancer therapeutics that target the PI3K pathway. Dr. Cantley and his colleague Marcus Goncalves, MD PhD are initiating a series of clinical trials to ask whether placing patients on a ketogenic diet, intended to alter the patients’ metabolism by reducing insulin resistance, can improve the efficacy of these drugs for patients with lymphoma, breast, or endometrial cancer. Dr. Cantley and Dr. Goncalves are both recipients of Mark Foundation grant funding to support their efforts to target key metabolic pathways in cancer.

Our second speaker, Marcia Haigis, PhD of Harvard Medical School, discussed another exciting angle on the effects of systemic metabolic alterations on cancer. Dr. Haigis demonstrated that obesity has a differential effect on tumor cells and the T cells tasked with controlling tumor growth – tumor cells respond to obesity by increasing the rate at which they burn fats for energy, which depletes fat from the local microenvironment. Increased uptake by tumor cells deprives T cells of fats, reducing their ability to suppress tumor growth. Excitingly, Dr. Haigis has identified several potential targets to improve cancer therapy for obese patients.

Rounding out the afternoon of exciting talks, Greg Delgoffe, PhD from University of Pittsburgh and a Mark Foundation Emerging Leader Award recipient shared his recent results that metabolic manipulations can improve the performance of cellular therapies for cancer. Cell therapies are an extraordinarily promising new class of treatments for cancer that involve extracting, expanding, and weaponizing immune cells outside the body, then infusing these cells into the patient to fight their tumor. Dr. Delgoffe has shown that a careful consideration of the metabolic conditions in which the cells are grown and expanded when outside the body can dramatically improve their anti-cancer function.

The groundbreaking work presented during the symposium and the stimulating panel discussion that followed, moderated by our Chief Scientific Officer Ryan Schoenfeld, PhD, underscore the therapeutic potential of drugs designed to disrupt the metabolic pathways of cancer cells and reduce any negative impacts on immune function. While clinical trials of some such drugs have initially fallen short of expectations, the results may say less about the promise of interventions that alter metabolic processes than they do about the need for deeper understanding of these complex pathways. Indeed, emerging research has identified further potential targets for therapy and continues to yield insights that will prove fruitful in improving diagnosis, predicting treatment response, and overcoming tumor resistance to therapy.

Although a virtual symposium can never fully replace the experience of meeting in person, the Mark Foundation symposium on cancer metabolism was a welcome chance to engage with the scientific community at a time when many researchers feel increasingly isolated. The Mark Foundation will host a second virtual symposium in the fall of 2021 on the topic of Metastasis – we hope you’ll join our mailing list or keep an eye on our website for the announcement and join us for what is sure to be another thrilling day of scientific talks and debate.

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