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

1. Prevent Insulin Resistance

Being in a state of insulin resistance can accelerate tumor growth in humans, highlighting the importance of metabolic health in cancer prevention and management.

2. Keep Insulin Levels Low

The ideal metabolic situation is to prevent insulin levels from getting high, as this can have detrimental effects on health, including accelerating tumor growth.

3. Prioritize Insulin Sensitivity

Focus on maintaining insulin sensitivity rather than just body mass index (BMI) for cancer risk, as insulin-resistant individuals (whether overweight or lean) show increased cancer risk.

4. Eliminate Sweet Drinks, Desserts

Based on empirical observation of the link between increased sugar consumption and obesity, eliminate sweet drinks and desserts from your diet.

5. Avoid Sugary Liquids

Consuming sugar in liquid form allows fructose to reach the colon, directly feeding polyp growth, whereas the same amount in solid food would be absorbed before reaching the colon.

6. Avoid Fructose-Glucose Mix

Colorectal polyps grow faster when both fructose and glucose are consumed together, with fructose driving the kinetics and glucose providing the carbon atoms for growth.

7. Reduce Sugar for Colon Health

High sugar consumption can significantly accelerate the growth and aggressiveness of colorectal polyps, even without causing obesity or insulin resistance, suggesting a direct feeding mechanism for tumor growth.

8. Beware Glucose-Fructose Combination

The natural combination of glucose and fructose, especially in liquid form, is uniquely problematic for health due to its chronic toxicity and ability to drive specific cancer growth.

9. Choose Whole Fruit Over Juice

The key difference in sugar consumption is whether it’s embedded in fibrous whole fruit (like an apple) or pure in water (like apple juice), as whole fruit slows absorption and prevents glucose spikes.

10. Eat Whole Fruit, Avoid Spikes

Eating whole fruit leads to slower sugar absorption and minimal glucose spikes, unlike fruit juice which causes rapid spikes, thus preventing high insulin release.

11. Manage Insulin Levels

When considering metabolic health, prioritize managing insulin levels, as high insulin is a key concern, even if glucose levels appear to be in line.

12. Recognize Insulin’s Cancer Role

Understand that high levels of insulin can drive the growth of cancer cells, a phenomenon observed in cell cultures for decades.

13. Pair PI3K Inhibitors with Diet/Drug

To maximize the efficacy of PI3 kinase inhibitors in shrinking tumors, combine them with either an SGLT2 inhibitor or a ketogenic diet (8% slow-release carb, 80% fat, 12% protein), as both dramatically lower insulin.

14. Ketogenic Diet or SGLT2

If you have cancer and are on a PI3 kinase inhibitor, a ketogenic diet is recommended for its effectiveness, but an SGLT2 inhibitor is a good, easier-to-take second-best option.

15. Ketogenic Diet Pre-Load

For optimal effectiveness when using a ketogenic diet with PI3 kinase inhibitors, begin the diet a full week prior to starting the inhibitor to deplete glycogen stores.

16. Combine KD with PI3K for Pancreatic Cancer

For pancreatic cancer (especially KRAS, P53 mutant types), a ketogenic diet alone or a PI3 kinase inhibitor alone may not be effective, but their combination can lead to complete tumor disappearance.

17. Avoid Insulin with PI3K Inhibitors

If undergoing cancer treatment with a PI3 kinase inhibitor and experiencing hyperglycemia, avoid insulin or insulin secretagogues, as these can raise serum insulin and reactivate tumor growth.

18. Metformin for Hyperglycemia

For patients on PI3 kinase inhibitors, metformin is the preferred method for managing hyperglycemia; if it’s insufficient, other insulin-raising treatments should be avoided.

19. Consider SGLT2 Inhibitors

SGLT2 inhibitors, which cause glucose to be excreted in the urine, are an effective way to lower both glucose and insulin levels.

20. Low-Carb Breakfast with PI3K Inhibitors

When taking PI3 kinase inhibitors, eat a low-carbohydrate, high-fat breakfast (e.g., scrambled eggs, avocado, high-fat yogurt with almonds) to limit toxicities, increase absorption, and avoid sugary items like juice or Ensure.

21. Maintain Strict Low-Carb Diet

To maximize the benefits of insulin-management strategies in cancer therapy, maintain a strict low-carbohydrate diet throughout the day, as even evening high-glucose meals can impact morning glucose and insulin levels.

22. Ketogenic Diet for Cancer: Supervise

Do not automatically adopt a ketogenic diet for cancer without medical supervision, as it may have adverse effects in certain cancer types (e.g., AML), even though it’s generally healthy for normal individuals.

23. Assess Tumor Insulin Receptors

Measuring insulin receptor levels on a tumor can help customize cancer therapy, as high levels may indicate a favorable response to approaches that manage insulin.

24. Restrict Serine/Methionine

For certain cancers and mutational backgrounds, restricting amino acids like serine or methionine in the diet can make specific drugs more effective by selectively depriving cancer cells of nucleotide precursors.

25. Embrace Diet-Drug Pairing

Recognize that combining specific dietary interventions with targeted drug therapies represents a significant and innovative frontier in cancer treatment.

26. Explore Pharmaceuticalized Diets

Consider pharmaceuticalized dietary interventions, such as precisely prepared meals with specific compositions, as a viable adjunct therapy for cancer patients to ensure adherence and optimize outcomes.

27. Oncologists Learn Cancer Metabolism

To improve cancer care, oncologists should deepen their understanding of cancer metabolism to effectively manage predictable complications of certain medications, such as hyperinsulinemia and hyperglycemia, which are desired features when using these drugs correctly.

28. Translate Science to Practice

Strive to translate scientific observations from the laboratory into practical changes in behavior, medical practice, drug metabolism, and diet to effectively address diseases like diabetes and cancer.

29. Investigate Unexpected Results

In scientific research, when you encounter an unexpected result, focus intensely on understanding the biochemical and chemical reasons behind it, as this is often where breakthroughs occur.

30. Embrace Confusing Results

When a result doesn’t make sense, view it as an exciting opportunity, as it often indicates a more complex underlying mechanism and can lead to significant breakthroughs if investigated thoroughly.

31. Teach Science via Discovery

When teaching science, focus on the process of discovery, the stories of experiments, and the thinking involved, rather than rote memorization of facts, to better engage and screen for interested scientists.

32. Advocate Anti-Sugar Policies

To combat high sugar consumption, consider public health strategies similar to those used for tobacco, such as reducing advertisements for sugary foods (especially to children) and implementing taxes to make sugar more expensive.

33. Explore Cancer Clinical Trials

If you or someone you know has stage four breast or endometrial cancer, look for enrollment information for the upcoming PI3 kinase alpha inhibitor trial from Petra Pharmaceuticals, which will be registered on clinicaltrials.gov.

34. Consult Your Physician

Always discuss combinations of therapies, including drugs for diabetes, cancer, and nutritional therapies, with your physician, as the podcast does not provide medical advice.