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A survey of open questions in adaptive therapy: Bridging mathematics and clinical translation, eLife, Review Article, Mar 23, 2023

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For those wanting to do a deep dive into Adaptive Theory, this survey paper is the current master document to do so. It includes the major researchers affiliated with Moffitt and others from around the globe and, as the title indicates, addresses current questions about applying these principles into clinical practice.

Research is linked throughout the paper, so additional depth can be easily found by investigating those sources.

The concept's foundational principle of maintaining "high levels of tumor burden to benefit from the competitive suppression of treatment- sensitive subpopulations on treatment-resistant subpopulations" runs counter to all SOC regimes I am aware of. It also recognizes that in some instances, the acceptance of such high tumor burdens could lead to outcomes similar to no treatment at all - when the tumor population continues to increase in spite of adaptive methodologies.

Because it discusses at length the issues and theoretical frameworks in play for cycled treatment vacations, it is an important paper for all those using vacations now or considering them for the future.

The Abstract is copied below and the full paper linked at the bottom. The posted diagram shows the relative nature of the eleven questions addressed in the paper:

Abstract

Adaptive therapy is a dynamic cancer treatment protocol that updates (or ‘adapts’) treatment decisions in anticipation of evolving tumor dynamics. This broad term encompasses many possible dynamic treatment protocols of patient-specific dose modulation or dose timing. Adaptive therapy maintains high levels of tumor burden to benefit from the competitive suppression of treatment-sensitive subpopulations on treatment-resistant subpopulations. This evolution-based approach to cancer treatment has been integrated into several ongoing or planned clinical trials, including treatment of metastatic castrate resistant prostate cancer, ovarian cancer, and BRAF-mutant melanoma. In the previous few decades, experimental and clinical investigation of adaptive therapy has progressed synergistically with mathematical and computational modeling. In this work, we discuss 11 open questions in cancer adaptive therapy mathematical modeling. The questions are split into three sections: (1) integrating the appropriate components into mathematical models (2) design and validation of dosing protocols, and (3) challenges and opportunities in clinical translation.

Full paper is here:

A survey of open questions in adaptive therapy: Bridging mathematics and clinical translation, eLife, Review Article, Cancer Biology, Medicine, Mar 23, 2023.

elifesciences.org/articles/...

Here is a link to the ANZadapt Phase II clinical trial mentioned in the paper. (This is an extension of the trial reported in the eLife paper linked by MateoBeach in a reply to an earlier post by RickyTarr, which is here:

healthunlocked.com/fight-pr...

Phase II Randomised Controlled Trial of Patient-specific Adaptive vs. Continuous Abiraterone or eNZalutamide in mCRPC (ANZadapt)

clinicaltrials.gov/ct2/show...

BTW, the eLife Magazine website is a very rich resource for research of all types. (thanks Pablo) Its homepage is here:

elifesciences.org/

Lots to absorb and much to consider. Good Luck & Good Health to All,

Ciao - Kaptin K9

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jdm3

You da man!

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cujoe in reply tojdm3

But the K9 terror cannot hold a candle to the Great SproutMaster SuperHero Captain Flyboy from the Pine Tree State. A true modern day Sky King . . .

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