Closed-loop control of tumor growth by means of anti-angiogenic administration

Area of Science:

• Mathematical biology
• Control theory
• Cancer research

Background:

• Tumor growth is influenced by angiogenic stimulation and inhibition.
• Effective tumor volume reduction requires precise anti-angiogenic administration.
• Existing models may not fully account for sampled measurements in control systems.

Purpose of the Study:

• To develop a closed-loop control law for tumor volume reduction using anti-angiogenic therapy.
• To design a state observer for nonlinear systems with discrete-time measurements.
• To investigate the robustness and performance of the control scheme in a simulated experimental setting.

Main Methods:

• A tumor growth model incorporating angiogenic dynamics was utilized.
• Output-feedback linearization theory and a nonlinear state observer were employed.
• A novel time-delay systems approach was applied for a continuous-time observer with sampled data.

Main Results:

• Simulations demonstrated promising performance in reducing tumor volume.
• The control scheme exhibited robustness against initial observer estimates and model parameter uncertainties.
• Effective control was achieved within experimentally relevant measurement sampling intervals.

Conclusions:

• The proposed control scheme offers an effective strategy for anti-angiogenic therapy.
• The integration of a nonlinear observer with sampled data enhances control system design.
• The model's structural properties allow independent tuning of control and observer parameters, facilitating practical application.