Bob Gatenby's Work on Adaptive Therapy

Bob Gatenby's Work on Adaptive Therapy

Great question! Dr. [removed] Gatenby is a leader in adaptive therapy — an innovative approach to cancer treatment based on evolutionary biology and game theory. Let me explain his key concepts based on the educational resources available.

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What is Adaptive Therapy?

Adaptive therapy is a treatment strategy that uses evolutionary and game theory principles to treat cancer more effectively. Instead of always giving the maximum tolerable dose (the highest amount a patient can tolerate), adaptive therapy adjusts treatment based on how the tumor responds.

The basic idea: Cancer cells evolve and develop resistance over time. Adaptive therapy aims to:

• Control the tumor population
• Reduce cumulative drug exposure
• Potentially improve survival with less toxicity

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How Adaptive Therapy Works (The Clinical Reasoning)

According to the CancerPatientLab Webinars on Evolutionary Treatment Strategy, Dr. [removed] explains that:

1. Cancer is a Nonlinear System

• Tumors don't behave predictably like simple biological systems
• Cancer cells constantly adapt and evolve resistance to treatments
• The same treatment given repeatedly will eventually fail as resistant cells emerge

2. The Problem with Standard Dosing

• Traditional cancer treatment uses "maximum tolerable dose" — giving the highest amount of drug a patient can safely handle
• This approach kills sensitive cancer cells quickly BUT also selects for resistant cells to survive and multiply
• Over time, the resistant population takes over, and the cancer returns

3. The Adaptive Strategy Instead, adaptive therapy:

• Gives treatment until the tumor shrinks significantly (e.g., PSA drops 50%)
• Stops treatment and monitors the patient
• Restarts treatment when the tumor begins to grow again
• Cycles this on-off pattern repeatedly

Why this works: By stopping treatment periodically, you allow sensitive cells to re-grow and compete with resistant cells. This prevents resistant cells from completely dominating the tumor population.

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Real-World Example: Abiraterone in Prostate Cancer

Dr. [removed] team tested adaptive therapy with abiraterone (a hormone therapy for castrate-resistant prostate cancer). According to the CancerPatientLab Webinars:

The Study:

• 17 patients received adaptive therapy (treatment on-off cycles based on PSA response)
• 16 patients received standard continuous dosing
• Both groups had similar starting characteristics

The Protocol:

• Give abiraterone until PSA drops to 50% of starting level
• Stop the drug
• Restart when PSA returns to pre-treatment level
• Repeat the cycle

Key Finding: Mathematical models predicted tumor control for 2-20 cycles, and the clinical results supported this adaptive approach.

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Bipolar Androgen Therapy (BAT): An Application of Adaptive Thinking

Dr. [removed] also commented on Bipolar Androgen Therapy, which applies similar evolutionary principles:

What is BAT?

• Alternates between high testosterone and low testosterone (androgen deprivation)
• "Shocks" prostate cancer cells by swinging between extremes
• Based on understanding which cancer cells are sensitive to testosterone

Example from the webinars: A patient (Bryce Olson) with heavily treated prostate cancer tried BAT:

• PSA dropped from 307 → 5 → 1.79 over successive cycles
• Liquid biopsies showed that certain resistant mutations were being eliminated
• The therapy exploited an "Achilles heel" in the tumor's evolutionary status

Important caveat from Dr. [removed]: While BAT showed dramatic initial response, he emphasized that:

• Small resistant populations likely remain
• Cycling therapies will eventually select for androgen-independent cells
• "There's no reason to be optimistic in the longer term. Prostate cancer is hard to eradicate."

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Key Principles of Adaptive Therapy

According to Dr. [removed] work:

| Principle | Explanation | |-----------|-------------| | Evolutionary Dynamics | Cancer cells evolve resistance; treatment must account for this | | Small Population Vulnerability | When tumor burden is low, resistant cells are vulnerable to extinction | | Oscillating Treatment | On-off cycles create a "nearly steady state" rather than continuous pressure | | Precision Medicine Beyond Genetics | Understanding tumor evolution reveals treatment vulnerabilities, not just genetic mutations | | Extinction Events | The final treatment to eliminate cancer may be different from what initially shrank it |

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Questions to Ask Your Oncologist

If you're interested in adaptive therapy approaches:

1. "Are there adaptive therapy clinical trials available for my cancer type?"
2. "How does my tumor's evolutionary history (prior treatments, resistance patterns) inform treatment decisions?"
3. "Could treatment cycling or intermittent dosing be appropriate for my situation?"
4. "What biomarkers or tests would help monitor whether my cancer is developing resistance?"
5. "How will we know when to switch treatments or adjust the strategy?"

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Important Context

Dr. [removed] adaptive therapy approach represents emerging research that challenges traditional "maximum tolerable dose" thinking. While promising, it's not yet standard of care for all cancer types. His work is being studied at major institutions like Johns Hopkins and is generating important new insights about cancer biology.

Your oncologist can discuss whether adaptive therapy principles might apply to your specific situation, cancer type, and treatment plan.

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Sources:

• CancerPatientLab Webinars: "An Evolutionary Treatment Strategy" (Bob Gatenby, MD)
• CancerPatientLab Webinars: "Bipolar Androgen Therapy" (Bryce Olson and Bob Gatenby)

This information is for educational purposes only. Always consult your healthcare team for personalized medical advice and decisions.