Opportunities and Challenges in Implementation of Multiparameter Single Cell Analysis Platforms for Clinical Translation
Abstract
The high‐content interrogation of single cells with platforms optimized for the multiparameter characterization of cells in liquid and solid biopsy samples can enable characterization of heterogeneous populations of cells ex vivo. Doing so will advance the diagnosis, prognosis, and treatment of cancer and other diseases. However, it is important to understand the unique issues in resolving heterogeneity and variability at the single cell level before navigating the validation and regulatory requirements in order for these technologies to impact patient care. Since 2013, leading experts representing industry, aca...
Source: Clinical and Translational Science - January 1, 2018 Category: Biomedical Science Authors: Susan M. Keating, D. Lansing Taylor, Anne L. Plant, E. David Litwack, Peter Kuhn, Emily J. Greenspan, Christopher M. Hartshorn, Caroline C. Sigman, Gary J. Kelloff, David D. Chang, Gregory Friberg, Jerry S. H. Lee, Keisuke Kuida Tags: REVIEW Source Type: research
Cytochrome P450 Genetic Variation Associated with Tamoxifen Biotransformation in American Indian and Alaska Native People
We examined variation in cytochrome P450 (CYP) genes (CYP2D6, CYP3A4, CYP3A5, and CYP2C9) and tamoxifen biotransformation in AIAN patients with breast cancer (n = 42) from the Southcentral Foundation in Alaska and the Confederated Salish and Kootenai Tribes in Montana. We tested for associations between CYP diplotypes and plasma concentrations of tamoxifen and metabolites. Only the CYP2D6 variation was significantly associated with concentrations of endoxifen (P = 0.0008) and 4‐hydroxytamoxifen (P = 0.0074), tamoxifen's principal active metabolites, as well as key metabolic ratios. The CYP2D6 was also the most significan...
Source: Clinical and Translational Science - January 1, 2018 Category: Biomedical Science Authors: Burhan A. Khan, Renee Robinson, Alison E. Fohner, LeeAnna I. Muzquiz, Brian D. Schilling, Julie A. Beans, Matthew J. Olnes, Laura Trawicki, Holly Frydenlund, Cindi Laukes, Patrick Beatty, Brian Phillips, Deborah Nickerson, Kevin Howlett, Denise A. Dillard Tags: ARTICLE Source Type: research
It's Time to Reverse our Thinking: The Reverse Translation Research Paradigm
(Source: Clinical and Translational Science)
Source: Clinical and Translational Science - January 1, 2018 Category: Biomedical Science Authors: Valentina Shakhnovich Tags: EDITORIAL Source Type: research
Challenges and Opportunities in Dose Finding in Oncology and Immuno ‐oncology
(Source: Clinical and Translational Science)
Source: Clinical and Translational Science - January 1, 2018 Category: Biomedical Science Authors: Yan Ji, Jin Y. Jin, David M. Hyman, Geoffrey Kim, Ajit Suri Tags: REVIEW Source Type: research
Physician Awareness of Immune Responses to Polyethylene Glycol ‐Drug Conjugates
Abstract
Antibodies against polyethylene glycol (PEG) can critically jeopardize the efficacy and safety of PEGylated therapeutics. For some PEG‐drugs, a sizeable fraction of patients develop anti‐PEG antibodies (APA), leading to reduced efficacy and potential adverse events. We surveyed physicians from several specialties to assess their awareness of APA. Overall, 83% of the physicians surveyed indicated that they have recently prescribed PEGylated drugs. Although 91% of respondents were aware of antidrug antibodies in general, only 22% were aware of APA responses. Further, there was limited awareness (35%) of PEG's in...
Source: Clinical and Translational Science - January 1, 2018 Category: Biomedical Science Authors: Morgan D. McSweeney, Zina C. Versfeld, Delesha M. Carpenter, Samuel K. Lai Tags: BRIEF REPORT Source Type: research
A Preclinical Population Pharmacokinetic Model for Anti ‐CD20/CD3 T‐Cell‐Dependent Bispecific Antibodies
Abstract
CD20 is a cell‐surface receptor expressed by healthy and neoplastic B cells and is a well‐established target for biologics used to treat B‐cell malignancies. Pharmacokinetic (PK) and pharmacodynamic (PD) data for the anti‐CD20/CD3 T‐cell‐dependent bispecific antibody BTCT4465A were collected in transgenic mouse and nonhuman primate (NHP) studies. Pronounced nonlinearity in drug elimination was observed in the murine studies, and time‐varying, nonlinear PK was observed in NHPs, where three empirical drug elimination terms were identified using a mixed‐effects modeling approach: i) a constant nonsatu...
Source: Clinical and Translational Science - January 1, 2018 Category: Biomedical Science Authors: Gregory Z. Ferl, Arthur Reyes, Liping L. Sun, Melissa Cheu, Amy Oldendorp, Saroja Ramanujan, Eric G. Stefanich Tags: ARTICLE Source Type: research
Mechanisms of Action and Clinical Development of Elotuzumab
Clinical and Translational Science, EarlyView. (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - December 22, 2017 Category: Biomedical Science Source Type: research
Application of a Dynamic Map for Learning, Communicating, Navigating, and Improving Therapeutic Development
Clinical and Translational Science,Volume 11, Issue 2, Page 166-174, March 2018. (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - December 22, 2017 Category: Biomedical Science Source Type: research
Mechanisms of Action and Clinical Development of Elotuzumab
Clinical and Translational Science, EarlyView. (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - December 22, 2017 Category: Biomedical Science Source Type: research
Application of a Dynamic Map for Learning, Communicating, Navigating, and Improving Therapeutic Development
Clinical and Translational Science,Volume 11, Issue 2, Page 166-174, March 2018. (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - December 22, 2017 Category: Biomedical Science Source Type: research
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Clinical and Translational Science, Ahead of Print. (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - December 22, 2017 Category: Biomedical Science Source Type: research
Mechanisms of Action and Clinical Development of Elotuzumab
(Source: Clinical and Translational Science)
Source: Clinical and Translational Science - December 22, 2017 Category: Biomedical Science Authors: David Ritchie, Marco Colonna Tags: REVIEW Source Type: research
Application of a Dynamic Map for Learning, Communicating, Navigating, and Improving Therapeutic Development
Abstract
Drug discovery and development is commonly schematized as a “pipeline,” and, although appreciated by drug developers to be a useful oversimplification, this cartology may perpetuate inaccurate notions of straightforwardness and is of minimal utility for process engineering to improve efficiency. To create a more granular schema, a group of drug developers, researchers, patient advocates, and regulators developed a crowdsourced atlas of the steps involved in translating basic discoveries into health interventions, annotated with the steps that are particularly prone to difficulty or failure. This Drug Discovery...
Source: Clinical and Translational Science - December 22, 2017 Category: Biomedical Science Authors: John A. Wagner, Andrew M. Dahlem, Lynn D. Hudson, Sharon F. Terry, Russ B. Altman, C. Taylor Gilliland, Christopher DeFeo, Christopher P. Austin Tags: ARTICLE Source Type: research
Reverse Translation of US Food and Drug Administration Reviews of Oncology New Molecular Entities Approved in 2011 –2017: Lessons Learned for Anticancer Drug Development
Clinical and Translational Science,Volume 11, Issue 2, Page 123-146, March 2018. (Source: Clinical and Translational Science)
Source: Clinical and Translational Science - December 19, 2017 Category: Biomedical Science Source Type: research
