Abstract
Current anticancer drug development still largely follows the classic designs developed for chemotherapeutic agents over the past 4 to 5 decades, remaining slow, costly, and inefficient, with continuing high risks of costly late drug attrition. A Pharmacologic Audit Trail has been described to decrease these risks, incorporating pharmacokinetic, pharmacodynamic, intermediate efficacy endpoints, as well as patient stratification molecular biomarkers. Molecular biomarker-based patient selection in hypothesis-testing early clinical trials is critical to clinically qualify putative predictive biomarkers for rationally designed, molecularly targeted drugs as early as possible. Nevertheless, major concerns have been raised about the impact of using such biomarkers in early trials, in view of the costs and time involved to develop multiple certified assays for clinical use. The rapid evolution of novel technologies of utility to this field, such as next-generation sequencing and circulating tumor-cell isolation, makes these valid concerns of critical importance. We therefore propose a more efficient parallel predictive biomarker and clinical anticancer drug development process to deal with the obstacles hindering progress.
References
Mar 9, 2006·Health Affairs·Christopher P Adams, Van V Brantner
Jul 29, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Pingfu FuMark Schluchter
Jun 11, 2010·Nature Reviews. Cancer·Timothy A YapJohann S de Bono
Oct 29, 2010·The New England Journal of Medicine·Eunice L KwakA John Iafrate
Jan 6, 2011·British Journal of Cancer·B BasuJ S de Bono
Citations
Nov 15, 2012·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·G ArgilésJ Tabernero
Apr 5, 2012·Nature Reviews. Clinical Oncology·Jordi RodónJosep Tabernero
Nov 22, 2013·Nucleic Acids Research·Ronnie P-A BerntssonPål Stenmark
Mar 17, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Richard L SchilskyBarbara A Conley
Mar 5, 2013·The Oncologist·Taofeek K Owonikoko
Jul 2, 2014·British Journal of Cancer·M OngJ S de Bono
Nov 29, 2015·Seminars in Oncology·Jorge Zeron-MedinaJordi Rodon
Aug 2, 2014·Molecular Oncology·Rodrigo DienstmannJosep Tabernero
Nov 26, 2014·Nature Reviews. Clinical Oncology·Armand de GramontStanley R Hamilton
Sep 25, 2016·Seminars in Oncology·Udai Banerji, Paul Workman
Jul 3, 2013·Human Reproduction·H ZhangW Y Zhang
May 10, 2013·Clinical Chemistry·Michael J Duffy, John Crown
Jan 20, 2018·Oncotarget·Gabriele GamerithArno Amann
Mar 16, 2013·Current Opinion in Oncology·Rodrigo DienstmannJosep Tabernero
Jan 1, 2012·American Society of Clinical Oncology Educational Book·Rodrigo DienstmannJosep Tabernero
Jul 25, 2019·The Cancer Journal·Deborah B Doroshow, James H Doroshow
Sep 26, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Victor Moreno GarcíaStan B Kaye