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Diet and Metabolic Therapeutics in Cancer

February 3–6, 2022

Chaired By

 Navdeep Chandel, PhD of Northwestern University
 Heather Christofk, PhD of UCLA
 Jason Locasale, PhD of Duke University

Meeting Description

Nutrition exerts profound effects on health, and dietary interventions are commonly used to treat diseases of metabolic etiology. Although cancer has a substantial metabolic component, the development of principles that define whether nutrition and new metabolic therapies may be used to influence tumor outcome are in the beginning stages. Nevertheless, it is also established that targeting metabolic pathways with longstanding chemotherapy agents or radiation can sometimes lead to controlled therapeutic outcomes. In contrast, whether specific dietary interventions could influence the metabolic pathways that are targeted in standard cancer therapies is not well known. Now, recent work has emerged showing that changes in caloric intake, macronutrient composition, and the balance of specific macronutrients in the diet also influence cancer.

For example, a diet high in fat and low carbohydrates can affect the outcome of tumors with defined mechanisms of dysregulated insulin signaling. We and others have shown that changes to the amino acid content in diets can influence metabolism related to the uptake of that nutrient in the tumor which in turn affects cancer outcomes by affecting the metabolic flux in a tumor-specific vulnerable metabolic pathway. Thus, there are emerging studies and mechanism linking nutrition and diet to cancer biology and therapy.

We propose to organize a Focus Meeting that brings together current and emerging leaders whose work bridges the nutrition-cancer interface to discuss their work in the new interdisciplinary field of ‘Nutrition and Cancer Metabolism’ and to explore its potential as a novel area for therapeutic intervention. We aim to bring together scientists who bring diverse perspectives to the table to discuss key questions in the field and identify important future directions.

Meeting Summary

The foundation hosted a hybrid virtual/in-person meeting at the beautiful Asilomar conference center in Pacific Grove CA. About two-thirds of the participants attended in-person and one-third attended virtually. It was chaired by Heather Christofk, PhD (UCLA), Navdeep Chandel, PhD (Northwestern University), and Jason Locasale, PhD (Duke University). Several of the virtual attendees participated almost throughout the entire meeting allowing for a highly interactive hybrid engagement. The meeting attendance included three new Forbeck Scholars, Allison Ringel, PhD, Robert Banh, PhD and Ana Gomes, PhD.

The meeting focused on cancer metabolism with an emphasis on therapy. The two general areas focused on the emerging area of diet and nutrition in cancer therapy and new areas of research in developing drugs that target the altered metabolism in cancers. Throughout the meeting there were talks on possibly modifying carbohydrate, fate and protein intake to influence cancer and both new drug targets as well as repurposing approved drugs such as the diabetes drugs metformin and the kidney glucose transporter inhibitor for cancer therapy.

The meeting opened with a session on diet and cancer, beginning with a talk by Lew Cantley, PhD who discussed his model of carbohydrate intake and Insulin signaling in cancer. Katy Wellen, PhD discussed dietary fructose and acetyl-coA sources for lipid synthesis including carnitine metabolism. Thales Papagiannakopoulos, PhD discussed ketogenic diets and their diverse effects on lung cancer progression and host toxicity including cachexia. Ana Gomes, PhD discussed methylmalonic acid in cancer and aging. It concluded with a presentation from Karen Vousden, PhD who discussed the possibilities of altering dietary changes to the amino acid serine in influencing cancer outcome. The next session developed the theme of metabolism and cell fate, an aspect of basic science linked to cancer metabolism and therapies. It began with Lydia Finley who discussed how the citric acid cycle can determine cell fate of embryonic cells. Kathrin Plath, PhD highlighted the role of tryptophan metabolism role in development. The session concluded with discussions on nutrient sensing by mTor from David Sabatini, MD and Jason Locasale, PhD who discussed methionine, another possible cancer dietary intervention with effects on cell fate and healthspan. The next day’s opening session focused on diet and tumor immunity. It was highlighted by several interesting conceptual talks including Lydia Lynch’s (PhD) work on dietary fat composition and its effects on cancer and the immune system and Allison Ringel’s (PhD) work on obesity and inflammation in cancer. Russell Jones and Sue Kaech, PhD discussed how metabolism controls function of T cells and macrophages, respectively. Chi Dang, MD, PhD discussed the importance of circadian rhythms and cellular pH controlling cancer progressiona and tumor immunity. The final session focused on metabolic therapeutics and began with Eileen White’s (PhD) work on targeting autophagy and cancer, brought up past concepts in the meeting including the use of metformin in cancer by Navdeep Chandel, PhD. Robert Banh, PhD discussed serine metabolism and protein translation. Heather Christofk, PhD, Ernst Lengyel, MD, PhD, and Ralph Deberardinis, MD, PhD discussed their efforts to investigate metabolism in cancer patients with implications for therapeutics. Overall, the meeting inspired a number of great discussions on emerging concepts in areas of nutrition, cancer and metabolism-based therapies. New work in the future including developing collaborations are anticipated.

Forum Participants

Robert Banh, PhD
New York University
 Forbeck Scholar

Yasmine Belkaid, PhD
National Institutes of Health

Lewis Cantley, PhD
Weill Cornell

Navdeep Chandel, PhD
Northwestern University

Heather Christofk, PhD
University of California, Los Angeles

Chi Dang, MD, PhD
The Wistar Institute

Ana Patricia Da Silva Gomes, PhD
H. Lee Moffitt Cancer Center
 Forbeck Scholar

Ralph Deberardinis, MD, PhD
UT Southwestern

Lydia Finley, PhD
Memorial Sloan Kettering Cancer Center

Cholsoon Jang, PhD
University of California Irvine

Russell Jones, PhD
Van Andel Institute

Sue Kaech, PhD
Salk Institute

Ernst Lengyel, MD, PhD
University of Chicago

Jason Locasale, PhD
Duke University

Lydia Lynch, PhD
Brigham and Womens Hospital, Harvard Medical School

Thales Papagiannakopoulos, PhD
NYU Langone

Kathrin Plath, PhD
University of California Los Angeles

Alison Ringel, PhD
Harvard Medical School
 Forbeck Scholar

David Sabatini, MD, PhD
MIT / Whitehead Institute

Karen Vousden, PhD
The Francis Crick Institute

Kathryn Wellen, PhD
University of Pennsylvania

Eileen White, PhD
Rutgers Cancer Institute