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Transport Oncophysics in silico, in vitro, and in vivo
This content has been downloaded from IOPscience. Please scroll down to see the full text. 2014 Phys. Biol. 11 060201 (http://iopscience.iop.org/1478-3975/11/6/060201) View the table of contents for this issue, or go to the journal homepage for more Download details: IP Address: 80.82.77.83 This content was downloaded on 28/08/2017 at 04:08 Please note that terms and conditions apply.
You may also be interested in: Intra-tumoral heterogeneity of gemcitabine delivery and mass transport in human pancreatic cancer Eugene J Koay, Flavio E Baio, Alexander Ondari et al. Cancerous epithelial cell lines shed extracellular vesicles with a bimodal size distribution that is sensitive to glutamine inhibition Steven Michael Santana, Marc A Antonyak, Richard A Cerione et al. Three-dimensional (3D) culture in sarcoma research and the clinical significance Songtao Gao, Jacson Shen, Francis Hornicek et al. Cell motility and ECM proteolysis regulate tumor growth and tumor relapse by altering the fraction of cancer stem cells and their spatial scattering Sandeep Kumar, Rahul Kulkarni and Shamik Sen Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients Carmen Ruiz, Julia Li, Madelyn S Luttgen et al. Dynamics of tumor growth and combination of anti-angiogenic and cytotoxic therapies M Kohandel, M Kardar, M Milosevic et al. Laser induced fluorescence spectroscopy of chemo-drugs as biocompatible fluorophores: irinotecan, gemcitabine and navelbine N S Hosseini Motlagh, P Parvin, F Ghasemi et al. Invasive cancer cells and metastasis Claudia Tanja Mierke
Physical Biology Phys. Biol. 11 (2014) 060201 (2pp)
doi:10.1088/1478-3975/11/6/060201
Preface
Transport Oncophysics in silico, in vitro, and in vivo Guest Editors Eugene J Koay Division of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA Mauro Ferrari Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Blvd., Houston TX 77030, USA
1478-3975/14/060201+02$33.00
The application of the physical sciences in oncology has generated tremendous interest in the scientific community and captured the attention of the general lay audience in recent years. Advances in nanotechnology, microvesicle characterization, mathematical modeling, and cancer imaging are several among many exciting frontiers in the physical sciences that hold promise in improving the human condition. A unifying principle that brings these diverse disciplines together is the concept of Transport Oncophysics, the understanding of mass transport differentials in cancer. To convey the depth and breadth of Oncophysics, we have assembled a group of leading experts in their fields, as we highlight how Oncophysics-related research can enable transformative developments in oncology. For example, Brian Kirby and his research group describe a novel phenomenon in the shedding of extracellular vesicles by cancer cell lines in a bimodal size distribution, whereby large-diameter microvesicle production is noted to be sensitive to a metabolic inhibitor of glutaminase [1]. Since extracellular shed vesicles (ESVs) may facilitate the metastatic niche in cancer, understanding the pathways that regulate their production is of keen interest. The connection between ESVs and altered cellular metabolism is a prime example of the major tenet of Transport Oncophysics: that multi-scale transport differentials (i.e., gradients of metabolites, chemotherapy, oxygen) between cellular compartments (e.g., DNA, organelles, cytosol, cellular membranes, extracellular matrix, and vasculature) distinguish malignant from normal cells and tissues. Furthermore, this distinguishing physical feature of cancer has important implications in its biological behavior. Dr Kirby’s group highlights how transport differentials in vesicles and metabolic pathways are linked, providing new insight into how the metastatic niche may be targeted for treatment. To fulfill the promise of targeted cancer treatments, however, it is important to understand the heterogeneity of cancer. To this end, our group has worked extensively with clinicians at MD Anderson Cancer Center to develop new ways of studying pancreatic cancer. In collaboration with Jason Fleming and associates, we build on previous work that showed significant inter-patient variability in gemcitabine delivery [2], now describing the intra-tumoral heterogeneity of gemcitabine delivery and mass transport in human pancreatic cancer [3]. This work emphasizes that intra-tumoral heterogeneity refers not only to the biology of cancer, but also the physics of cancer, as we observed that the delivery of drug to cancer cells in humans was highly variable between patients and within their tumors. In support of the Oncophysics view of multi-scale transport deregulation, we discovered that mass transport properties, derived from CT scans, can accurately and reproducibly describe the delivery of drug to cancer cells, and that this delivery prediction was modified when accounting for the expression level of the cellular transporter of gemcitabine: human equilibrative nucleoside transporter 1 (hENT1). Again, the multi-scale transport properties of human cancer influence an important aspect of therapeutic efficacy: drug delivery.
1
© 2014 IOP Publishing Ltd Printed in the UK
Phys. Biol. 11 (2014) 060201
Preface
Toward personalized predictions of drug response that account for the multiple deranged pathways that occur in cancer cells, Chih-Ming Ho and his group describe how the optimization of drug mixtures can be performed using a Feedback System Control technique [4]. The multi-dimensional scale of the cancer problem—as Dr Ho and associates point out—is one that necessitates the targeting of more than one deranged pathway to increase the probability of successful therapy. They describe a low order, smooth response surface of cells to multiple drugs in a spectrum of disease states. This approach could be used for multiple medical scenarios, and has clear utility in oncology, where inter-patient variability in drug response is a major challenge. As related to Transport Oncophysics, this important contribution of Dr Ho and associates illustrates how quantitative analysis of complex multi-dimensional systems can yield tangible solutions. The application of Transport Oncophysics to drug delivery and response is well illustrated in the works of Dr Fleming’s and Dr Ho’s groups, respectively. Bernhard Schrefler and associates show another application of the principles of Oncophysics, whereby the multiphasic nature of tumors is considered in a tumor growth model [5]. While prior tumor growth models do not incorporate the extracellular matrix (ECM) or consider it as a rigid structure, this new, elegant work pushes the boundaries of current growth models by incorporating the deformability of the ECM. They find that a deformable ECM has a different growth pattern than a rigid ECM, revealing how porosity may affect tumor growth. This new model agrees well with experimental data, emphasizing the importance of correct representations of the tumor microenvironment and its physical properties. The maligned differential mass transport properties of tumors influence a multitude of processes and tumor behaviors, including tumor growth, metastasis, and response to therapy. Collectively, the original works in this special issue of Physical Biology demonstrate some of the important applications of Transport Oncophysics. We see how this concept can be integrated into basic science, mathematical modeling, and clinical trials. Each of these studies speaks to the tailoring of cancer diagnosis and treatment toward the individual. This is inherently the strength of the Oncophysics concept: each one of us is the sum of a multiplicity of transport differentials. Understanding the disorganization of these differentials in cancer opens a realm of possibilities in all aspects of oncologic research. Moreover, with the increasing prevalence of tailored biological treatments for cancer, the integration of these Oncophysics approaches may enable truly novel diagnostic and therapeutic strategies to improve patient outcomes. References [1] Santana S M, Antonyak M A, Cerione R A and Kirby B J 2014 Cancerous epithelial cell lines shed extracellular vesicles in a bimodal size distribution that is sensitive to glutamine inhibition Phys. Bio. 56 065001 [2] Koay E J et al 2014 Transport properties of pancreatic cancer describe gemcitabine delivery and response J. Clin. Invest. 124 1525–36 [3] Koay E J et al 2014 Intra-tumoral heterogeneity in gemcitabine delivery and mass transport in human pancreatic cancer Phys. Bio. 56 065002 [4] Ding X et al 2014 Discovery of a low order drug-response surface for applications in personalized medicine Phys. Bio. 56 065003 [5] Sciumè G, Santagiuliana R, Ferrari M, Decuzzi P and Schrefler B 2014 A tumor growth model with deformable ECM Phys. Bio. 56 065004
2
Search
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About
Contact us
My IOPscience
Transport Oncophysics in silico, in vitro, and in vivo
This content has been downloaded from IOPscience. Please scroll down to see the full text. 2014 Phys. Biol. 11 060201 (http://iopscience.iop.org/1478-3975/11/6/060201) View the table of contents for this issue, or go to the journal homepage for more Download details: IP Address: 80.82.77.83 This content was downloaded on 28/08/2017 at 04:08 Please note that terms and conditions apply.
You may also be interested in: Intra-tumoral heterogeneity of gemcitabine delivery and mass transport in human pancreatic cancer Eugene J Koay, Flavio E Baio, Alexander Ondari et al. Cancerous epithelial cell lines shed extracellular vesicles with a bimodal size distribution that is sensitive to glutamine inhibition Steven Michael Santana, Marc A Antonyak, Richard A Cerione et al. Three-dimensional (3D) culture in sarcoma research and the clinical significance Songtao Gao, Jacson Shen, Francis Hornicek et al. Cell motility and ECM proteolysis regulate tumor growth and tumor relapse by altering the fraction of cancer stem cells and their spatial scattering Sandeep Kumar, Rahul Kulkarni and Shamik Sen Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients Carmen Ruiz, Julia Li, Madelyn S Luttgen et al. Dynamics of tumor growth and combination of anti-angiogenic and cytotoxic therapies M Kohandel, M Kardar, M Milosevic et al. Laser induced fluorescence spectroscopy of chemo-drugs as biocompatible fluorophores: irinotecan, gemcitabine and navelbine N S Hosseini Motlagh, P Parvin, F Ghasemi et al. Invasive cancer cells and metastasis Claudia Tanja Mierke
Physical Biology Phys. Biol. 11 (2014) 060201 (2pp)
doi:10.1088/1478-3975/11/6/060201
Preface
Transport Oncophysics in silico, in vitro, and in vivo Guest Editors Eugene J Koay Division of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA Mauro Ferrari Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Blvd., Houston TX 77030, USA
1478-3975/14/060201+02$33.00
The application of the physical sciences in oncology has generated tremendous interest in the scientific community and captured the attention of the general lay audience in recent years. Advances in nanotechnology, microvesicle characterization, mathematical modeling, and cancer imaging are several among many exciting frontiers in the physical sciences that hold promise in improving the human condition. A unifying principle that brings these diverse disciplines together is the concept of Transport Oncophysics, the understanding of mass transport differentials in cancer. To convey the depth and breadth of Oncophysics, we have assembled a group of leading experts in their fields, as we highlight how Oncophysics-related research can enable transformative developments in oncology. For example, Brian Kirby and his research group describe a novel phenomenon in the shedding of extracellular vesicles by cancer cell lines in a bimodal size distribution, whereby large-diameter microvesicle production is noted to be sensitive to a metabolic inhibitor of glutaminase [1]. Since extracellular shed vesicles (ESVs) may facilitate the metastatic niche in cancer, understanding the pathways that regulate their production is of keen interest. The connection between ESVs and altered cellular metabolism is a prime example of the major tenet of Transport Oncophysics: that multi-scale transport differentials (i.e., gradients of metabolites, chemotherapy, oxygen) between cellular compartments (e.g., DNA, organelles, cytosol, cellular membranes, extracellular matrix, and vasculature) distinguish malignant from normal cells and tissues. Furthermore, this distinguishing physical feature of cancer has important implications in its biological behavior. Dr Kirby’s group highlights how transport differentials in vesicles and metabolic pathways are linked, providing new insight into how the metastatic niche may be targeted for treatment. To fulfill the promise of targeted cancer treatments, however, it is important to understand the heterogeneity of cancer. To this end, our group has worked extensively with clinicians at MD Anderson Cancer Center to develop new ways of studying pancreatic cancer. In collaboration with Jason Fleming and associates, we build on previous work that showed significant inter-patient variability in gemcitabine delivery [2], now describing the intra-tumoral heterogeneity of gemcitabine delivery and mass transport in human pancreatic cancer [3]. This work emphasizes that intra-tumoral heterogeneity refers not only to the biology of cancer, but also the physics of cancer, as we observed that the delivery of drug to cancer cells in humans was highly variable between patients and within their tumors. In support of the Oncophysics view of multi-scale transport deregulation, we discovered that mass transport properties, derived from CT scans, can accurately and reproducibly describe the delivery of drug to cancer cells, and that this delivery prediction was modified when accounting for the expression level of the cellular transporter of gemcitabine: human equilibrative nucleoside transporter 1 (hENT1). Again, the multi-scale transport properties of human cancer influence an important aspect of therapeutic efficacy: drug delivery.
1
© 2014 IOP Publishing Ltd Printed in the UK
Phys. Biol. 11 (2014) 060201
Preface
Toward personalized predictions of drug response that account for the multiple deranged pathways that occur in cancer cells, Chih-Ming Ho and his group describe how the optimization of drug mixtures can be performed using a Feedback System Control technique [4]. The multi-dimensional scale of the cancer problem—as Dr Ho and associates point out—is one that necessitates the targeting of more than one deranged pathway to increase the probability of successful therapy. They describe a low order, smooth response surface of cells to multiple drugs in a spectrum of disease states. This approach could be used for multiple medical scenarios, and has clear utility in oncology, where inter-patient variability in drug response is a major challenge. As related to Transport Oncophysics, this important contribution of Dr Ho and associates illustrates how quantitative analysis of complex multi-dimensional systems can yield tangible solutions. The application of Transport Oncophysics to drug delivery and response is well illustrated in the works of Dr Fleming’s and Dr Ho’s groups, respectively. Bernhard Schrefler and associates show another application of the principles of Oncophysics, whereby the multiphasic nature of tumors is considered in a tumor growth model [5]. While prior tumor growth models do not incorporate the extracellular matrix (ECM) or consider it as a rigid structure, this new, elegant work pushes the boundaries of current growth models by incorporating the deformability of the ECM. They find that a deformable ECM has a different growth pattern than a rigid ECM, revealing how porosity may affect tumor growth. This new model agrees well with experimental data, emphasizing the importance of correct representations of the tumor microenvironment and its physical properties. The maligned differential mass transport properties of tumors influence a multitude of processes and tumor behaviors, including tumor growth, metastasis, and response to therapy. Collectively, the original works in this special issue of Physical Biology demonstrate some of the important applications of Transport Oncophysics. We see how this concept can be integrated into basic science, mathematical modeling, and clinical trials. Each of these studies speaks to the tailoring of cancer diagnosis and treatment toward the individual. This is inherently the strength of the Oncophysics concept: each one of us is the sum of a multiplicity of transport differentials. Understanding the disorganization of these differentials in cancer opens a realm of possibilities in all aspects of oncologic research. Moreover, with the increasing prevalence of tailored biological treatments for cancer, the integration of these Oncophysics approaches may enable truly novel diagnostic and therapeutic strategies to improve patient outcomes. References [1] Santana S M, Antonyak M A, Cerione R A and Kirby B J 2014 Cancerous epithelial cell lines shed extracellular vesicles in a bimodal size distribution that is sensitive to glutamine inhibition Phys. Bio. 56 065001 [2] Koay E J et al 2014 Transport properties of pancreatic cancer describe gemcitabine delivery and response J. Clin. Invest. 124 1525–36 [3] Koay E J et al 2014 Intra-tumoral heterogeneity in gemcitabine delivery and mass transport in human pancreatic cancer Phys. Bio. 56 065002 [4] Ding X et al 2014 Discovery of a low order drug-response surface for applications in personalized medicine Phys. Bio. 56 065003 [5] Sciumè G, Santagiuliana R, Ferrari M, Decuzzi P and Schrefler B 2014 A tumor growth model with deformable ECM Phys. Bio. 56 065004
2
