Tissue transport affects how treatment scheduling increases the efficacy of chemotherapeutic drugs

Ganz, Dan E.; Sexton-Stallone, Briana; Brackett, Emily L.; Forbes, Neil S.

doi:10.1016/j.jtbi.2017.10.022

Cited by 2 publications

(1 citation statement)

References 29 publications

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“…Drugs unable to efficiently penetrate the tissue are not capable of clearing regions far from the vascular network although they can kill cells in a culture 33 . Additionally, the characteristics of a drug—diffusivity, associating rate, and systemic clearance rate—determine its capability to penetrate solid tumors 34 , 35 . Additionally, there have been many computational attempts to examine the effects of different drug parameters on the efficacy of drug delivery 23 , 32 , 35 , 36 , but their impact on successive treatment cycles have not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

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

Kashkooli

Soltani

2021

Sci Rep

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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.

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