Modelling of Tirapazamine Effects on Solid Tumour Morphology
Bioreductive drugs are in clinical practice to exploit the resistance from tumour microenvironments especially in the hypoxic region of tumour. We presented a tumour treatment model to capture the pharmacology of one of the most prominent bioreductive drugs, Tirapazamine (TPZ) which is in clinical trials I and II. We calculated solid tumour mass in our previous work and then integrated that model with TPZ infusion. We calculated TPZ cytotoxicity, concentration, penetration with increasing distance from blood vessel and offered resistance from microenvironments for drug penetration inside the tumour while considering each cell as an individual entity. The impact of these factors on tumour morphology is also showed to see the drug behaviour inside animals/humans tumours. We maintained the heterogeneity factors in presented model as observed in real tumour mass especially in terms of cells proliferation, cell movement, extracellular matrix (ECM) interaction, and the gradients of partial oxygen pressure (pO2) inside tumour cells during the whole growth and treatment activity. The results suggest that TPZ high concentration in combination with chemotherapy should be given to get maximum abnormal cell killing. This model can be a good choice for oncologists and researchers to explore more about TPZ action inside solid tumour.
KeywordsAQ4N Extra Cellular Matrix Hypoxia and Tirapazamine
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