Back to Journals » OncoTargets and Therapy » Volume 6

Drugs for solid cancer the productivity crisis prompts a rethink

Authors Rösel D, Brábek J, Veselý P, Fernandes M

Received 13 March 2013

Accepted for publication 7 May 2013

Published 26 June 2013 Volume 2013:6 Pages 767—777

DOI https://doi.org/10.2147/OTT.S45177

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Video abstract presented by Jan Brábek.

Views: 173

Daniel Rösel,1 Jan Brábek,1 Pavel Veselý,2 Michael Fernandes3

1Department of Cell Biology, Charles University in Prague, Prague, Czech Republic; 2Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic; 3Medbase, Chapel Hill, NC, USA

Abstract: Despite remarkable progress in cancer-drug discovery, the delivery of novel, safe, and sustainably effective products to the clinic has stalled. Using Src as a model, we examine key steps in drug development. The preclinical evidence on the relationship between Src and solid cancer is in sharp contrast with the modest anticancer effect noted in conventional clinical trials. Here, we consider Src inhibitors as an example of a promising drug class directed to invasion and metastasis and identify roadblocks in translation. We question the assumption that a drug-induced tumor shrinkage in preclinical and clinical studies predicts a successful outcome. Our analysis indicates that the key areas requiring attention are related, and include preclinical models (in vitro and mouse models), meaningful clinical trial end points, and an appreciation of the role of metastasis in morbidity and mortality. Current regulations do not reflect the natural history of the disease, and may be unrelated to the key complications: local invasion, metastasis, and the development of resistance. Alignment of preclinical and clinical studies and regulations based on mechanistic trial end points and platforms may help in overcoming these roadblocks. Viewed kaleidoscopically, most elements necessary and sufficient for a novel translational paradigm are in place.

Keywords: cancer, paradigms, Src inhibitors, metastasis, translation, drug resistance

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]