Dataset Information

Illuminating the Numbers: Integrating Mathematical Models to Optimize Photomedicine Dosimetry and Combination Therapies.

ABSTRACT: Cancer photomedicine offers unique mechanisms for inducing local tumor damage with the potential to stimulate local and systemic anti-tumor immunity. Optically-active nanomedicine offers these features as well as spatiotemporal control of tumor-focused drug release to realize synergistic combination therapies. Achieving quantitative dosimetry is a major challenge, and dosimetry is fundamental to photomedicine for personalizing and tailoring therapeutic regimens to specific patients and anatomical locations. The challenge of dosimetry is perhaps greater for photomedicine than many standard therapies given the complexity of light delivery and light-tissue interactions as well as the resulting photochemistry responsible for tumor damage and drug-release, in addition to the usual intricacies of therapeutic agent delivery. An emerging multidisciplinary approach in oncology utilizes mathematical and computational models to iteratively and quantitively analyze complex dosimetry, and biological response parameters. These models are parameterized by preclinical and clinical observations and then tested against previously unseen data. Such calibrated and validated models can be deployed to simulate treatment doses, protocols, and combinations that have not yet been experimentally or clinically evaluated and can provide testable optimal treatment outcomes in a practical workflow. Here, we foresee the utility of these computational approaches to guide adaptive therapy, and how mathematical models might be further developed and integrated as a novel methodology to guide precision photomedicine.

SUBMITTER: Spring BQ

PROVIDER: S-EPMC6529192 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Illuminating the Numbers: Integrating Mathematical Models to Optimize Photomedicine Dosimetry and Combination Therapies.

Spring Bryan Q BQ Lang Ryan T RT Kercher Eric M EM Rizvi Imran I Wenham Robert M RM Conejo-Garcia José R JR Hasan Tayyaba T Gatenby Robert A RA Enderling Heiko H

Frontiers in physics 20190402

Cancer photomedicine offers unique mechanisms for inducing local tumor damage with the potential to stimulate local and systemic anti-tumor immunity. Optically-active nanomedicine offers these features as well as spatiotemporal control of tumor-focused drug release to realize synergistic combination therapies. Achieving quantitative dosimetry is a major challenge, and dosimetry is fundamental to photomedicine for personalizing and tailoring therapeutic regimens to specific patients and anatomica ...[more]

PMID: 31123672

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Project description:The number of publications on mathematical modeling of cancer is growing at an exponential rate, according to PubMed records, provided by the US National Library of Medicine and the National Institutes of Health. Seminal papers have initiated and promoted mathematical modeling of cancer and have helped define the field of mathematical oncology (Norton and Simon in J Natl Cancer Inst 58:1735-1741, 1977; Norton in Can Res 48:7067-7071, 1988; Hahnfeldt et al. in Can Res 59:4770-4775, 1999; Anderson et al. in Comput Math Methods Med 2:129-154, 2000. https://doi.org/10.1080/10273660008833042 ; Michor et al. in Nature 435:1267-1270, 2005. https://doi.org/10.1038/nature03669 ; Anderson et al. in Cell 127:905-915, 2006. https://doi.org/10.1016/j.cell.2006.09.042 ; Benzekry et al. in PLoS Comput Biol 10:e1003800, 2014. https://doi.org/10.1371/journal.pcbi.1003800 ). Following the introduction of undergraduate and graduate programs in mathematical biology, we have begun to see curricula developing with specific and exclusive focus on mathematical oncology. In 2018, 218 articles on mathematical modeling of cancer were published in various journals, including not only traditional modeling journals like the Bulletin of Mathematical Biology and the Journal of Theoretical Biology, but also publications in renowned science, biology, and cancer journals with tremendous impact in the cancer field (Cell, Cancer Research, Clinical Cancer Research, Cancer Discovery, Scientific Reports, PNAS, PLoS Biology, Nature Communications, eLife, etc). This shows the breadth of cancer models that are being developed for multiple purposes. While some models are phenomenological in nature following a bottom-up approach, other models are more top-down data-driven. Here, we discuss the emerging trend in mathematical oncology publications to predict novel, optimal, sometimes even patient-specific treatments, and propose a convention when to use a model to predict novel treatments and, probably more importantly, when not to.

Project description:As antimicrobial resistance increases, it is crucial to develop new treatment strategies to counter the emerging threat. In this paper, we consider combination therapies involving conventional antibiotics and debridement, coupled with a novel anti-adhesion therapy, and their use in the treatment of antimicrobial resistant burn wound infections. Our models predict that anti-adhesion-antibiotic-debridement combination therapies can eliminate a bacterial infection in cases where each treatment in isolation would fail. Antibiotics are assumed to have a bactericidal mode of action, killing bacteria, while debridement involves physically cleaning a wound (e.g. with a cloth); removing free bacteria. Anti-adhesion therapy can take a number of forms. Here we consider adhesion inhibitors consisting of polystyrene microbeads chemically coupled to a protein known as multivalent adhesion molecule 7, an adhesin which mediates the initial stages of attachment of many bacterial species to host cells. Adhesion inhibitors competitively inhibit bacteria from binding to host cells, thus rendering them susceptible to removal through debridement. An ordinary differential equation model is developed and the antibiotic-related parameters are fitted against new in vitro data gathered for the present study. The model is used to predict treatment outcomes and to suggest optimal treatment strategies. Our model predicts that anti-adhesion and antibiotic therapies will combine synergistically, producing a combined effect which is often greater than the sum of their individual effects, and that anti-adhesion-antibiotic-debridement combination therapy will be more effective than any of the treatment strategies used in isolation. Further, the use of inhibitors significantly reduces the minimum dose of antibiotics required to eliminate an infection, reducing the chances that bacteria will develop increased resistance. Lastly, we use our model to suggest treatment regimens capable of eliminating bacterial infections within clinically relevant timescales.

Dataset Information

Illuminating the Numbers: Integrating Mathematical Models to Optimize Photomedicine Dosimetry and Combination Therapies.

Publications

Illuminating the Numbers: Integrating Mathematical Models to Optimize Photomedicine Dosimetry and Combination Therapies.

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