Evaluation of solid tumor response to sequential treatment cycles via a new computational hybrid approach

Abstract

The development of an in silico approach that evaluates and identifies appropriate treatment protocols for individuals could help grow personalized treatment and increase cancer patient lifespans. With this motivation, the present study introduces a novel approach for sequential treatment cycles based on simultaneously examining drug delivery, tumor growth, and chemotherapy efficacy. This model incorporates the physical conditions of tumor geometry, including tumor, capillary network, and normal tissue assuming real circumstances, as well as the intravascular and interstitial fluid flow, drug concentration, chemotherapy efficacy, and tumor recurrence. Three treatment approaches—maximum tolerated dose (MTD), metronomic chemotherapy (MC), and chemo-switching (CS)—as well as different chemotherapy schedules are investigated on a real tumor geometry extracted from image. Additionally, a sensitivity analysis of effective parameters of drug is carried out to evaluate the potential of using different other drugs in cancer treatment. The main findings are: (i) CS, MC, and MTD have the best performance in reducing tumor cells, respectively; (ii) multiple doses raise the efficacy of drugs that have slower clearance, higher diffusivity, and lower to medium binding affinities; (iii) the suggested approach to eradicating tumors is to reduce their cells to a predetermined rate through chemotherapy and then apply adjunct therapy.

Active Tumor-Targeting Nano-formulations Containing Simvastatin and Doxorubicin Inhibit Melanoma Growth and Angiogenesis

“…The TME plays a compelling role in cancer development, by providing a complex and dynamic stage for bidirectional interactions between tumor and immune cells in favor of progression and metastasis ( Baghban et al, 2020 ). Thus, specifically targeting different key players within the TME at different time points, as well as optimal dosages and frequency of administration, is a crucial factor in achieving maximum drug benefit to the patient ( Moradi Kashkooli and Soltani, 2021 ). TAMs are the dominant immune cell type in the TME, representing up to 30–50% of tumor tissue and playing major roles in tumor angiogenesis growth, invasion, and immunosuppression ( Banciu et al, 2008c ; Patras et al, 2016 ; Luput et al, 2017 ; Rauca et al, 2018 ; Licarete et al, 2019 ; Ge and Ding, 2020 ; Licarete et al, 2020 ).…”

Computational Modeling of Combination of Magnetic Hyperthermia and Temperature-Sensitive Liposome for Controlled Drug Release in Solid Tumor

“…The model can be further developed by incorporating different injection strategies; these include an intravenous administration of TSLs or magnetic liposomes through continuous injection, direct injection of both MNPs and TSLs into the tumor, and intratumoral injection of chemotherapy drugs. The current model for microvascular transport can be extended to incorporate a more realistic vascular network as demonstrated by Kashkooli and Soltani [92]. In addition, specific cell killing models for different types of cancer cells and anticancer drugs could be employed to make the prediction more tumor specific.…”

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

“…The model was performed with a macroscopic point of view, and variations over the microscopic scale were average. Accordingly, for analyzing the function of normalization, the effect of anti-angiogenic therapy on transport properties of the interstitium was considered instead of including the tumor microvascular network by mathematical simulation [26] or image processing [27,74] under the influence of anti-angiogenesis. Another assumption is that the model was assumed to be 2D axisymmetric because there is one image of the tumor.…”

“…Drug delivery was studied in a comprehensive multi-scale model, in which the tumor-induced capillary network was performed by a mathematical model [26]. In the study of Moradi Kashkooli and Soltani [27], the importance of alternative chemotherapy strategies-metronomic chemotherapy and chemo-switching-in consecutive treatments were addressed compared to the conventional approach, which is based on maximum tolerated dose, through a numerical model on a real image of solid tumor. They proposed an appropriate computational framework to evaluate and improve the treatment efficacy of solid tumors.…”