Numerical Investigation on the Anti-Angiogenic Therapy-Induced Normalization in Solid Tumors

Area of Science:

• Biomedical Engineering
• Computational Biology
• Cancer Research

Background:

• Anti-angiogenic therapy normalizes tumor vasculature, impacting drug delivery.
• Solid tumors exhibit complex non-homogeneous structures (necrotic, vascularized regions).
• Understanding fluid flow and solute transport is crucial for effective chemotherapy.

Purpose of the Study:

• To numerically analyze fluid flow and solute transport in solid tumors under anti-angiogenic therapy normalization.
• To investigate the influence of normalization intensity and tumor size on drug delivery.
• To examine the long-term effects of normalization on drug uptake in necrotic tumor regions.

Main Methods:

• Numerical simulation of fluid flow and solute transport.
• Modeling of non-homogeneous solid tumors with varying vascularization.
• Inclusion of different chemotherapeutic agents (IgG, F(ab')2, F(ab')) and normalization intensities.
• Analysis of interstitial fluid pressure (IFP) and interstitial fluid velocity (IFV).

Main Results:

• Normalization reduces IFP, increasing interstitial fluid velocity in inner tumor regions.
• Normalization decreases drug washout from the tumor periphery.
• Improved solute concentration distribution in the tumor interstitium was observed.
• Normalization efficiency is dependent on tumor size, drug type, and normalization intensity.

Conclusions:

• Normalization can enhance drug delivery into non-homogeneous solid tumors.
• For large tumors, F(ab') is suggested with anti-angiogenic therapy to improve drug reservoir behavior.
• For small tumors, IgG is recommended, with normalization enhancing uniform exposure by 22%.
• Findings offer insights for optimizing adjuvant normalization strategies in preclinical and clinical trials.