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Tumor Drug Penetration Measurements Could Be the Neglected Piece of the Personalized Cancer Treatment Puzzle.
Bartelink, Imke H; Jones, Ella F; Shahidi-Latham, Sheerin K; Lee, Pei Rong Evelyn; Zheng, Yanan; Vicini, Paolo; van 't Veer, Laura; Wolf, Denise; Iagaru, Andrei; Kroetz, Deanna L; Prideaux, Brendan; Cilliers, Cornelius; Thurber, Greg M; Wimana, Zena; Gebhart, Geraldine.
Affiliation
  • Bartelink IH; Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Jones EF; Clinical Pharmacology, Pharmacometrics and DMPK (CPD), MedImmune, South San Francisco, California, USA.
  • Shahidi-Latham SK; Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, Vrije Universiteit Amsterdam, The Netherlands.
  • Lee PRE; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California, USA.
  • Zheng Y; Drug Metabolism & Pharmacokinetics, Genentech, South San Francisco, California, USA.
  • Vicini P; Department of Laboratory Medicine of the UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
  • van 't Veer L; Clinical Pharmacology, Pharmacometrics and DMPK (CPD), MedImmune, South San Francisco, California, USA.
  • Wolf D; Clinical Pharmacology, Pharmacometrics and DMPK (CPD), MedImmune, Cambridge, UK.
  • Iagaru A; Department of Laboratory Medicine of the UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
  • Kroetz DL; Department of Laboratory Medicine of the UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
  • Prideaux B; Division of Nuclear Medicine and Molecular Imaging at Stanford Health Care, Stanford, California, USA.
  • Cilliers C; Department of Bioengineering and Therapeutic Sciences (BTS), School of Pharmacy, University of California, San Francisco, San Francisco, California, USA.
  • Thurber GM; Rutgers New Jersey Medical School, Public Health Research Institute, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA.
  • Wimana Z; Departments of Chemical Engineering and Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
  • Gebhart G; Departments of Chemical Engineering and Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Clin Pharmacol Ther ; 106(1): 148-163, 2019 07.
Article in En | MEDLINE | ID: mdl-30107040
Precision medicine aims to use patient genomic, epigenomic, specific drug dose, and other data to define disease patterns that may potentially lead to an improved treatment outcome. Personalized dosing regimens based on tumor drug penetration can play a critical role in this approach. State-of-the-art techniques to measure tumor drug penetration focus on systemic exposure, tissue penetration, cellular or molecular engagement, and expression of pharmacological activity. Using in silico methods, this information can be integrated to bridge the gap between the therapeutic regimen and the pharmacological link with clinical outcome. These methodologies are described, and challenges ahead are discussed. Supported by many examples, this review shows how the combination of these techniques provides enhanced patient-specific information on drug accessibility at the tumor tissue level, target binding, and downstream pharmacology. Our vision of how to apply tumor drug penetration measurements offers a roadmap for the clinical implementation of precision dosing.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Precision Medicine / Neoplasms / Antineoplastic Agents Type of study: Prognostic_studies Limits: Humans Language: En Journal: Clin Pharmacol Ther Year: 2019 Document type: Article Affiliation country: United States Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Precision Medicine / Neoplasms / Antineoplastic Agents Type of study: Prognostic_studies Limits: Humans Language: En Journal: Clin Pharmacol Ther Year: 2019 Document type: Article Affiliation country: United States Country of publication: United States