#110 - Lew Cantley, Ph.D.: Cancer metabolism, cancer therapies, and the discovery of PI3K

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May 11, 2020

Lew Cantley, a leading cancer biologist and director at Weill Cornell Medical College, delves into his groundbreaking discovery of PI3K, crucial for cancer treatment. He discusses the relationship between sugar consumption, insulin resistance, and tumor growth, revealing the surprising influences of dietary choices on cancer progression. Lew also highlights his innovative clinical trial for stage 4 cancer patients and how synergizing ketogenic diets with PI3K inhibitors can enhance treatment efficacy, reshaping the future of cancer therapies.

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INSIGHT

Cancer's Metabolic Needs

Cancer requires altered metabolism to switch from quiescence to a dividing state.
To divide and grow, cancer cells must increase glucose and amino acid uptake for anabolic processes.

ANECDOTE

West Virginia's Obesity Shift

Lew Cantley observed West Virginia transition from a state with very low obesity rates in the 1950s to high rates in the 60s and 70s.
He attributes this change to the introduction of high-fructose corn syrup and the increased consumption of sugary drinks.

INSIGHT

Insulin Resistance and Cancer

Insulin resistance, leading to elevated insulin levels, can accelerate tumor growth.
Cancer cells often have more insulin receptors, making them more responsive to insulin's growth-promoting effects.

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In this episode, Lew Cantley, Professor of cancer biology and Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medical College in NYC, walks us through his amazing discovery of phosphoinositide 3-kinase (PI3K) and the implications for the care of patients with cancer. He explains various combinations of therapies being tested and used, including the possibility of pairing prescriptive nutritional therapies to increase the efficacy of drugs like PI3K inhibitors. Lew also explains the metabolic nature of cancer through the lens of his research into the connection between sugar consumption, insulin resistance, and tumor growth. Additionally, Lew provides some details about his exciting new clinical trial that is just now enrolling patients with stage 4 breast cancer and endometrial cancer.

We discuss:

Teaching science through the lens of discovery—A better approach to learning science [5:15];
The metabolic nature of cancer, mitochondria, and a more nuanced explanation of the Warburg Effect [8:30];
The observation that convinced Lew to stop eating sugar [20:15];
The connection between obesity, insulin resistance, and cancer [25:30];
Sugar consumption and tumor growth—What did Lew’s 2019 paper find? [32:00];
Natural sugar vs. HFCS, fruit vs. fruit juice, insulin response and cancer growth [43:00];
Increasing efficacy of PI3K inhibitors with ketogenic diets, SGLT2 inhibitors, and metformin [53:30];
Lew’s clinical trial enrolling stage 4 breast cancer and endometrial cancer patients [1:07:30];
Pairing diet with drug could be the future of cancer treatment [1:09:30];
PI3K inhibitors on the market, alpha vs. delta isoform, and the possibility of pairing them with a food prescription [1:16:15];
What questions will Lew be focused on in the next chapter of his career? [1:22:15];
Lew's early work that ultimately led to the discovery of PI3K [1:27:30];
Studying the mechanism by which mitochondria make ATP [1:30:45];
How understanding the mechanism by which insulin drove glucose uptake into a cell got Lew closer to finding PI3K [1:38:15];
How Lew knew PI3K was important in driving the growth of cancer cells [1:55:00];
Lew’s unlikely observation of phosphorylation at the 3' position of the inositol ring resulting in the formation of phosphatidylinositol-3-phosphate [1:59:00]; and
More.

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