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Manolio T.A.,Human Genome Research Institutes | Abramowicz M.,Free University of Colombia | Al-Mulla F.,Kuwait University | Anderson W.,National Health and Medical Research Council | And 40 more authors.
Science Translational Medicine | Year: 2015

Around the world, innovative genomic-medicine programs capitalize on singular capabilities arising from local health care systems, cultural or political milieus, and unusual selected risk alleles or disease burdens. Such individual eforts might beneft from the sharing of approaches and lessons learned in other locales. The U.S. National Human Genome Research Institute and the National Academy of Medicine recently brought together 25 of these groups to compare projects, to examine the current state of implementation and desired near-term capabilities, and to identify opportunities for collaboration that promote the responsible practice of genomic medicine. Eforts to coalesce these groups around concrete but compelling signature projects should accelerate the responsible implementation of genomic medicine in eforts to improve clinical care worldwide. © 2015, American Association for the Advancement of Science. All rights reserved.

Abernethy A.,Duke University | Abrahams E.,Personalized Medicine Coalition | Barker A.,Arizona State University | Buetow K.,Arizona State University | And 11 more authors.
Clinical Cancer Research | Year: 2014

An ever-expanding understanding of the molecular basis of the more than 200 unique diseases collectively called cancer, combined with efforts to apply these insights to clinical care, is forming the foundation of an era of personalized medicine that promises to improve cancer treatment. At the same time, these extraordinary opportunities are occurring in an environment of intense pressure to contain rising healthcare costs. This environment presents a challenge to oncology research and clinical care, because both are becoming progressively more complex and expensive, and because the current tools to measure the cost and value of advances in care (e.g., comparative effectiveness research, cost-effectiveness analysis, and health technology assessments) are not optimized for an ecosystem moving toward personalized, patient-centered care. Reconciling this tension will be essential to maintaining progress in a cost-constrained environment, especially because emerging innovations in science (e.g., increasing identification of molecular biomarkers) and in clinical process (implementation of a learning healthcare system) hold potential to dramatically improve patient care, and may ultimately help address the burden of rising costs. For example, the rapid pace of innovation taking place within oncology calls for increased capability to integrate clinical research and care to enable continuous learning, so that lessons learned from each patient treated can inform clinical decision making for the next patient. Recognizing the need to define the policies required for sustained innovation in cancer research and care in an era of cost containment, the stakeholder community must engage in an ongoing dialogue and identify areas for collaboration. This article reflects and seeks to amplify the ongoing robust discussion and diverse perspectives brought to this issue by multiple stakeholders within the cancer community, and to consider how to frame the research and regulatory policies necessary to sustain progress against cancer in an environment of constrained resources. © 2014 AACR.

Hertz D.L.,University of Michigan | McLeod H.L.,DeBartolo Family Personalized Medicine Institute
Clinical Pharmacology and Therapeutics | Year: 2016

Tumor genome analysis is transforming cancer treatment by enabling identification of specific oncogenic drivers and selection of effective targeted agents. Meanwhile, patient genome analysis is being employed across therapeutic areas to inform selection of appropriate drugs and doses for treatment safety. Integration of patient genome analysis concurrent with preemptive tumor genetic testing will enable oncologists to make informed treatment decisions to select the right dose of the right drug for each patient and their tumor. © 2015 ASCPT.

Shain K.H.,H. Lee Moffitt Cancer Center and Research Institute | Dalton W.S.,H. Lee Moffitt Cancer Center and Research Institute | Dalton W.S.,DeBartolo Family Personalized Medicine Institute | Tao J.,University of South Florida
Oncogene | Year: 2015

B-cell tumorigenesis results from a host of known and unknown genetic anomalies, including non-random translocations of genes that normally function as determinants of cell proliferation or cell survival to regions juxtaposed to active immunoglobulin heavy chain enhancer elements, chromosomal aneuploidy, somatic mutations that further affect oncogenic signaling and loss of heterozygosity of tumor-suppressor genes. However, it is critical to recognize that even in the setting of a genetic disease, the B-cell/plasma cell tumor microenvironment (TME) contributes significantly to malignant transformation and pathogenesis. Over a decade ago, we proposed the concept of cell adhesion-mediated drug resistance to delineate a form of TME-mediated drug resistance that protects hematopoietic tumor cells from the initial effect of diverse therapies. In the interim, it has been increasingly appreciated that TME also contributes to tumor initiation and progression through sustained growth/proliferation, self-renewal capacity, immune evasion, migration and invasion as well as resistance to cell death in a host of B-cell malignancies, including mantle cell lymphoma, diffuse large B-cell lymphoma, Waldenstroms macroglobulinemia, chronic lymphocytic leukemia and multiple myeloma. Within this review, we propose that TME and the tumor co-evolve as a consequence of bidirectional signaling networks. As such, TME represents an important target and should be considered integral to tumor progression and drug response. © 2015 Macmillan Publishers Limited.

Jia F.-F.,Central South University | Tan Z.-R.,Central South University | McLeod H.L.,Central South University | McLeod H.L.,DeBartolo Family Personalized Medicine Institute | And 3 more authors.
Xenobiotica | Year: 2016

1.The primary objective of this study was to evaluate the effects of quercetin on the pharmacokinetics of cefprozil. The secondary objective was to evaluate the safety of the combined use of cefprozil and quercetin. 2.An open-label, two-period, crossover phase I trial among 24 Han Chinese male subjects was conducted. Participants were given 500 mg of quercetin orally once daily for 15 d followed by single dose of cefprozil (500 mg) on day 15. Serum concentrations of cefprozil were then measured in all participants on day 15. A 15-d washout period was then assigned after which a 500 mg dose of cefprozil was administered and measured in the serum on day 36. 3.All subjects completed the trial, and no serious adverse events were reported. We measured mean serum concentrations of cefprozil in the presence and absence of quercetin in all participants. The maximum serum concentration of cefprozil in the presence of quercetin was 8.18 ug/ml (95% CI: 7.55–8.81) versus a maximum cefprozil concentration of 8.35 ug/ml (95% CI: 7.51–9.19) in the absence of quercetin. We conclude that the concurrent use of quercetin has no substantial effect on serum concentrations of orally administered cefprozil. 4.Co-administration of quercetin showed no statistically significant effects on the pharmacokinetics of cefprozil in healthy Chinese subjects. © 2016 Taylor & Francis.

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