Anti-angiogenic drug scheduling optimisation with application to colorectal cancer

Abstract

Bevacizumab (bvz) is a first choice anti-angiogenic drug in oncology and is primarily administered in combination with chemotherapy. It has been hypothesized that anti-angiogenic drugs enhance efficacy of cytotoxic drugs by “normalizing” abnormal tumor vessels and improving drug penetration. Nevertheless, the clinical relevance of this phenomenon is still unclear with several studies over recent years suggesting an opposing relationship. Herein, we sought to develop a new computational tool to interrogate anti-angiogenic drug scheduling with particular application in the setting of colorectal cancer (CRC). Specifically, we have employed a mathematical model of vascular tumour growth which interrogates the impact of anti-angiogenic treatment and chemotherapeutic treatment on tumour volume. Model predictions were validated using CRC xenografts which underwent treatment with a clinically relevant combinatorial anti-angiogenic regimen. Bayesian model selection revealed the most appropriate term for capturing the effect of treatments on the tumour size, and provided insights into a switch-like dependence of FOLFOX delivery on the tumour vasculature. Our experimental data and mathematical model suggest that delivering chemotherapy prior to bvz may be optimal in the colorectal cancer setting.

System-based approaches as prognostic tools for glioblastoma

“…A key idea is the shift from real-world clinical trial testing a single treatment option on many, mostly unselected, patients to first test in silico several treatment options, both approved or repurposed, for each individual patient. Importantly, mathematical models can also optimize the dosage and scheduling of the selected treatment [141, 162, 164–166].…”

Immune Checkpoint Inhibitor-Based Combination Therapy for Colorectal Cancer: An Overview

“…In addition to inhibiting the VEGF/VEGFR pathway, TKI drugs may also inhibit targets related to immune regulation, such as platelet-derived growth factor receptor (PDGFR), angiopoietin-2 receptor (TIE2), and colony-stimulating factor 1 receptor, and have stronger synergy with immunotherapy. [92][93][94] EGFR EGFR is a member of the epidermal growth factor receptor (HER) family, which includes HER1 (erbB1, EGFR), HER2 (erbB2, NEU), HER3 (erbB3), and HER4 (erbB4). 95,96 Studies have shown that EGFR is overexpressed or abnormally expressed in many solid tumors.…”

“…In addition to inhibiting the VEGF/VEGFR pathway, TKI drugs may also inhibit targets related to immune regulation, such as platelet-derived growth factor receptor (PDGFR), angiopoietin-2 receptor (TIE2), and colony-stimulating factor 1 receptor, and have stronger synergy with immunotherapy. 92–94 …”

Effect of energy requirements in the growth of brain tumor: a theoretical approach

“…Such models are incredibly important to correlate the clinical and experimental data with tumor growth patterns, and to evaluate the efficacy of a newer treatment before clinical intervention [1][2][3][4][5][6]. Predicting the effectiveness of radiotherapy in cancer treatment and optimization of anti-angiogenic drug scheduling can be carried out using mathematical models [7,8].…”