On systems and control approaches to therapeutic gain

Area of Science:

• Mathematical oncology
• Control theory in medicine
• Cancer systems biology

Background:

• Increasing development of mathematical models for cancer processes.
• Need for conceptual frameworks to guide new treatment designs based on these models.

Purpose of the Study:

• To formulate two distinct therapeutic gain strategies using a modern control perspective.
• To provide a framework for developing novel cancer treatment approaches.

Main Methods:

• Application of a modern control theory perspective.
• Formulation of two conceptually distinct therapeutic gain strategies.
• Abstraction of strategies for specific cancer types (MMR-deficient cancers, BCR-ABL pro-B cell leukemia).

Main Results:

• A direct strategy aims to selectively kill cancer cells over normal cells.
• An indirect strategy seeks to improve outcomes by shifting cancer cell states toward those of curable cases.
• The direct strategy links anti-cancer agents to cell death, exemplified by iodinated uridine (IUdR) for MMR-deficient cancers.
• The indirect strategy requires models connecting drugs to survival determinants, abstracting from childhood leukemia treatment.

Conclusions:

• Cancer therapeutic gain problem formulations define the scope of cancer process modeling.
• Abstracting these formulations aids in considering alternative treatment strategies.
• These frameworks support synthesizing learning experiences across diverse cancer types.