What does physics have to do with cancer?

Michor, Franziska; Liphardt, Jan; Ferrari, Mauro; Widom, Jonathan

doi:10.1038/nrc3092

Cited by 169 publications

(143 citation statements)

References 139 publications

(147 reference statements)

Supporting

Mentioning

132

Contrasting

Unclassified

Order By: Relevance

“…Solid tumors, such as PDAC, often have mass transport properties that differ from those of normal tissues (5)(6)(7)(8)(9)(10)(11). PDAC exhibits several pathological features that can be considered physical barriers to effective drug delivery, including disorganized, leaky, and nonfunctional vasculature (12)(13)(14); characteristically dense stroma (9); and deregulated cellular transport proteins (15).…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we hypothesized that multiscale transport phenomena (6)(7)(8) influence delivery of and response to gemcitabinebased therapy in human PDAC. We studied transport phenomena in human PDAC by using the pancreatic protocol CT scans of patients and conducting a first-in-kind clinical trial of intraoperative gemcitabine infusion during curative resection of PDAC.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Transport properties of pancreatic cancer describe gemcitabine delivery and response

Koay

Truty²,

Cristini³

et al. 2014

J. Clin. Invest.

Self Cite

162

156

View full text Add to dashboard Cite

Background. The therapeutic resistance of pancreatic ductal adenocarcinoma (PDAC) is partly ascribed to ineffective delivery of chemotherapy to cancer cells. We hypothesized that physical properties at vascular, extracellular, and cellular scales influence delivery of and response to gemcitabine-based therapy.Methods. We developed a method to measure mass transport properties during routine contrast-enhanced CT scans of individual human PDAC tumors. Additionally, we evaluated gemcitabine infusion during PDAC resection in 12 patients, measuring gemcitabine incorporation into tumor DNA and correlating its uptake with human equilibrative nucleoside transporter (hENT1) levels, stromal reaction, and CT-derived mass transport properties. We also studied associations between CT-derived transport properties and clinical outcomes in patients who received preoperative gemcitabine-based chemoradiotherapy for resectable PDAC.Results. Transport modeling of 176 CT scans illustrated striking differences in transport properties between normal pancreas and tumor, with a wide array of enhancement profiles. Reflecting the interpatient differences in contrast enhancement, resected tumors exhibited dramatic differences in gemcitabine DNA incorporation, despite similar intravascular pharmacokinetics. Gemcitabine incorporation into tumor DNA was inversely related to CT-derived transport parameters and PDAC stromal score, after accounting for hENT1 levels. Moreover, stromal score directly correlated with CT-derived parameters. Among 110 patients who received preoperative gemcitabine-based chemoradiotherapy, CT-derived parameters correlated with pathological response and survival.Conclusion. Gemcitabine incorporation into tumor DNA is highly variable and correlates with multiscale transport properties that can be derived from routine CT scans. Furthermore, pretherapy CT-derived properties correlate with clinically relevant endpoints.Trial registration. Clinicaltrials.gov NCT01276613.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transport properties of pancreatic cancer describe gemcitabine delivery and response

Koay

Truty²,

Cristini³

et al. 2014

J. Clin. Invest.

Self Cite

162

156

View full text Add to dashboard Cite

show abstract

“…In transport oncophysics [124,125], cancer is defined as a proliferative disease of mass transport deregulation which manifests itself primarily in the disruption of the biological barriers that separate body compartments [126]. The most important consequences of this deregulation are invasion, the ability to 'push' its way into host tissue; metastasis, the ability to move to distant locations; and angiogenesis, upsetting the balance of nutrient distribution and elimination of metabolites [126].…”

Section: Multi-phase Computational Modelling For Predicting Tumour Grmentioning

confidence: 99%

USNCTAM perspectives on mechanics in medicine

Bao

Bazilevs

Chung

et al. 2014

J. R. Soc. Interface.

Self Cite

View full text Add to dashboard Cite

Over decades, the theoretical and applied mechanics community has developed sophisticated approaches for analysing the behaviour of complex engineering systems. Most of these approaches have targeted systems in the transportation, materials, defence and energy industries. Applying and further developing engineering approaches for understanding, predicting and modulating the response of complicated biomedical processes not only holds great promise in meeting societal needs, but also poses serious challenges. This report, prepared for the US National Committee on Theoretical and Applied Mechanics, aims to identify the most pressing challenges in biological sciences and medicine that can be tackled within the broad field of mechanics. This echoes and complements a number of national and international initiatives aiming at fostering interdisciplinary biomedical research. This report also comments on cultural/educational challenges. Specifically, this report focuses on three major thrusts in which we believe mechanics has and will continue to have a substantial impact. (i) Rationally engineering injectable nano/microdevices for imaging and therapy of disease. Within this context, we discuss nanoparticle carrier design, vascular transport and adhesion, endocytosis and tumour growth in response to therapy, as well as uncertainty quantification techniques to better connect models and experiments. (ii) Design of biomedical devices, including point-of-care diagnostic systems, model organ and multi-organ microdevices, and pulsatile ventricular assistant devices. (iii) Mechanics of cellular processes, including mechanosensing and mechanotransduction, improved characterization of cellular constitutive behaviour, and microfluidic systems for single-cell studies.

show abstract

“…Such innovations have allowed nanoparticle-based chemotherapeutics to show enhanced efficacy over freely administered drugs. Improving our understanding of how nanoparticles interact with the mononuclear phagocyte system is key to developing more effective delivery strategies, particularly for cancer and other diseases characterized by pathological disruptions of mass transport 35 .…”

Section: Visualization Of Nanoparticle Transport and Uptake In The Livermentioning

confidence: 99%

Real-time intravital microscopy of individual nanoparticle dynamics in liver and tumors of live mice

Ven¹,

Yun²,

Kim³

et al. 2013

Protocol Exchange

Self Cite

View full text Add to dashboard Cite

Intravital microscopy is emerging as an important experimental tool for the research and development of multi-functional therapeutic nanoconstructs. The direct visualization of nanoparticle dynamics within live animals provides invaluable insights into the mechanisms that regulate nanotherapeutics transport and cell-particle interactions. Here we present a protocol to image the dynamics of nanoparticles within the liver and tumors of live mice immediately following systemic injection using a high-speed (30-400 fps) confocal or multi-photon laserscanning fluorescence microscope. Techniques for quantifying the real-time accumulation and cellular association of individual particles with a size ranging from several tens of nanometers to micrometers are described, as well as an experimental strategy for labeling Kupffer cells in the liver in vivo. Experimental design considerations and controls are provided, as well as minimum equipment requirements. The entire protocol takes approximately 4-8 hours and yields quantitative information. These techniques can serve to study a wide range of kinetic parameters that drive nanotherapeutics delivery, uptake, and treatment response.

show abstract

What does physics have to do with cancer?

Cited by 169 publications

References 139 publications

Transport properties of pancreatic cancer describe gemcitabine delivery and response

Transport properties of pancreatic cancer describe gemcitabine delivery and response

USNCTAM perspectives on mechanics in medicine

Real-time intravital microscopy of individual nanoparticle dynamics in liver and tumors of live mice

Contact Info

Product

Resources

About