Spatial Modeling of Drug Delivery Routes for Treatment of Disseminated Ovarian Cancer.

@article{Winner2016SpatialMO,
  title={Spatial Modeling of Drug Delivery Routes for Treatment of Disseminated Ovarian Cancer.},
  author={Kimberly R. Kanigel Winner and Mara P. Steinkamp and Rebecca Jane Lee and Maciej H. Swat and Carolyn Y. Muller and Melanie E. Moses and Yi Jiang and Bridget S. Wilson},
  journal={Cancer research},
  year={2016},
  volume={76 6},
  pages={
          1320-1334
        }
}
In ovarian cancer, metastasis is typically confined to the peritoneum. Surgical removal of the primary tumor and macroscopic secondary tumors is a common practice, but more effective strategies are needed to target microscopic spheroids persisting in the peritoneal fluid after debulking surgery. To treat this residual disease, therapeutic agents can be administered by either intravenous or intraperitoneal infusion. Here, we describe the use of a cellular Potts model to compare tumor penetration… 
Mathematical modeling of intraperitoneal drug delivery: simulation of drug distribution in a single tumor nodule
TLDR
The developed parametrical CFD model is a powerful tool providing more insight in the drug transport and penetration during IP chemotherapy, and demonstrates the importance of the drug that is used for therapy.
Multi-scale models of ovarian cancer
TLDR
A cellular Potts simulation integrated data at multiple scales to model microscopic residual disease during relapse after a primary surgery and generated new hypotheses about tumor cell behavior, and the effectiveness of drug delivery to tumors disseminated in the peritoneal cavity.
Albumin-based cancer therapeutics for intraperitoneal drug delivery: a review
TLDR
Data from recent (pre)clinical trials suggest that IP albumin-bound chemotherapy may result in superior efficacy in the treatment of peritoneal metastasis compared to standard chemotherapy formulations.
Penetration Efficiency of Antitumor Agents in Ovarian Cancer Spheroids: The Case of Recombinant Targeted Toxin DARPin-LoPE and the Chemotherapy Drug, Doxorubicin
TLDR
The low penetration of the targeted toxin into spheroid was shown along with a significant decrease in its efficiency against the three-dimensional tumor spheoid as compared with the two-dimensional monolayer culture.
Micropharmacology: An In Silico Approach for Assessing Drug Efficacy Within a Tumor Tissue
TLDR
The proposed modeling approach takes into account the explicit tumor tissue morphology, its metabolic landscape and/or specific receptor distribution, which can be assessed from patients’ diagnostic biopsies and developed into a tool suitable for personalized medicine, such as neoadjuvant chemotherapy.
Modelling drug transport during intraperitoneal chemotherapy
TLDR
A distinction is made between three different types of model: the lumped parameter model, the distributed model and the cell-based model for IP chemotherapy: which steps of the transport process are included and where assumptions are made.
Establishment of a rat ovarian peritoneal metastasis model to study pressurized intraperitoneal aerosol chemotherapy (PIPAC)
TLDR
A reproducible and efficient rodent model is proposed to study PIPAC and ePIPAC in OC xenografts with widespread PM to characterize and optimize pharmacokinetic and biophysical parameters, and to evaluate the anti-cancer efficacy of (e)PIPac treatment.
Pharmacovigilance of Local Chemotherapy in the Peritoneum
TLDR
Performing intraperitoneal chemotherapy requires additional vigilance for surgeon and gynecologists, and a basic knowledge of pharmacokinetics and pharmacodynamics of intra peritoneal application is necessary.
New Treatment Modalities for the Management of Peritoneal Metastases
TLDR
An overview of the rationale, methodology, and preliminary results of experimental and clinical studies evaluating these new locoregional therapies for the management of PM is provided here.
Towards personalized computational oncology: from spatial models of tumour spheroids, to organoids, to tissues
TLDR
This review is a survey of mathematical models that explicitly take into account the spatial architecture of three-dimensional tumours and address tumour development, progression and response to treatments and discusses models of epithelial acini, multicellular spheroids, normal and tumourSpheroids and organoids, and multi-component tissues.
...
1
2
3
4
...

References

SHOWING 1-10 OF 58 REFERENCES
A mechanistic compartmental model for total antibody uptake in tumors.
TLDR
A simple mechanistic model of antibody uptake and retention is presented that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization.
Multicellular spheroids in ovarian cancer metastases: Biology and pathology.
TLDR
The key biological features of spheroids are outlined, specifically discussing their role in EOC dissemination and chemo-response as well as providing insights into spheroid functionality.
A theoretical model for intraperitoneal delivery of cisplatin and the effect of hyperthermia on drug penetration distance.
TLDR
A theoretical model for the intraperitoneal (i.p.) delivery of cisplatin and heat to tumor metastases in tissues adjacent to the peritoneal cavity shows that exchange with the microvasculature has more effect than cellular uptake in limiting the penetration distance, and suggests that use of sodium thiosulfate to deactivate systemic cis Platin may be counterproductive when heat is delivered locally.
A mathematical model of doxorubicin penetration through multicellular layers.
TLDR
A mathematical model based upon the premise that the transport of doxorubicin across cell membrane bilayers occurs by a passive "flip-flop" mechanism of the drug between two membrane leaflets was constructed and demonstrates good agreement between predicted and actual drug penetration in vitro.
Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer.
TLDR
The results of this meta-analysis provide the most reliable estimates of the relative survival benefits of IP over IV therapy and should be used as part of this decision making process.
Ovarian Tumor Attachment, Invasion, and Vascularization Reflect Unique Microenvironments in the Peritoneum: Insights from Xenograft and Mathematical Models
TLDR
The integrated in vivo mouse model and computer simulations provide a unique platform for evaluating targeted therapies for ovarian cancer relapse and indicate that invasion is strongly influenced by features underlying the mesothelial lining at different sites, but is also affected by local production of chemotactic factors.
Current Advances in Mathematical Modeling of Anti-Cancer Drug Penetration into Tumor Tissues
TLDR
This review describes how various types of models were used to predict spatio-temporal distributions of drugs within the tumor tissue, to simulate different ways to overcome barriers to drug transport, or to optimize treatment schedules.
A Systems Approach for Tumor Pharmacokinetics
TLDR
A framework for categorizing primary pharmacokinetics of drugs in tumors is developed and described and drugs are classified into four categories depending on whether uptake is limited by blood flow, extravasation, interstitial diffusion, or local binding and metabolism.
Drug resistance and the solid tumor microenvironment.
TLDR
How the tumor microenvironment may be involved in the resistance of solid tumors to chemotherapy and potential strategies to improve the effectiveness of drug treatment by modifying factors relating to the tumormicroenvironment are described.
Intraperitoneal chemotherapy in the first‐line treatment of women with stage III epithelial ovarian cancer
TLDR
The results from this review indicated that cisplatin‐containing intraperitoneal chemotherapy should be offered to patients on the basis of significant improvements in overall survival, and specific aspects of the treatment, such as optimal agent, dose, and scheduling are needed.
...
1
2
3
4
5
...