A survey of open questions in adaptive therapy: bridging mathematics and clinical translation

TL;DR

This paper reviews key open questions in the mathematical modeling of adaptive cancer therapy, highlighting challenges in model components, protocol design, and clinical translation to improve personalized treatment strategies.

Contribution

It systematically identifies and discusses 11 open questions in adaptive therapy modeling, bridging mathematical theory and clinical application.

Findings

Identifies 11 open questions in adaptive therapy modeling.

Highlights challenges in designing and validating dosing protocols.

Discusses opportunities for clinical translation of adaptive therapy models.

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) the necessary components of mathematical models of adaptive therapy 2) design and validation of dosing protocols, and 3) challenges and opportunities in clinical translation.