Avid Bioservices Inc (CDMO)

[biopharm]

Dr. Bruce Chabner : Peregrine Pharmaceuticals KOL :

Pharmacodynamic Biomarkers: Falling Short of the Mark?

Justin F. Gainor 1,
Dan L. Longo 2, and
Bruce A. Chabner 1

- Author Affiliations

1Department of Medicine, Massachusetts General Hospital Cancer Center; and
2Department of Medicine, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts

Corresponding Author:
Justin F. Gainor, Massachusetts General Hospital, 10 North Grove Street, LRH-2, Boston, MA 02114. Phone: [phone]; Fax: [phone]; E-mail: [e-mail]


Received January 31, 2014.
Revision received March 7, 2014.
Accepted March 21, 2014.

Abstract

In recent years, the clinical development of targeted therapies has been advanced by a greater understanding of tumor biology and genomics. Nonetheless, drug development remains a slow and costly process. An additional challenge is that targeted therapies may benefit only a subset of patients treated—typically those patients whose tumors are dependent on the target of interest. Thus, there is a growing need for the incorporation of both predictive and pharmacodynamic (PD) biomarkers in drug development. Predictive biomarkers are important to help guide patient selection, while PD biomarkers can provide information on the pharmacologic effects of a drug on its target. PD studies may provide insights into proof of mechanism (i.e., Does the agent hit its intended target?) and proof of concept (i.e., Does hitting the drug target result in the desired biologic effect?). PD studies may also provide information on the optimal biologic dosing or scheduling of a targeted agent. Herein, we review PD endpoints in the context of targeted drug development in non–small cell lung cancer, highlighting some of the key challenges encountered to date. In doing so, we discuss recent experiences with repeat tumor biopsies, surrogate tissue analysis, alternative clinical trial designs (e.g., window-of-opportunity trials), circulating biomarkers, and mechanism-based toxicity assessments. The application of such technologies and biomarkers in early clinical trials may facilitate rational drug development, while enhancing our understanding of why certain targeted therapies succeed or fail.

http://clincancerres.aacrjournals.org/content/20/10/2587.abstract

Looks like Genentech is into pre-clinical biomarkers. They must be aware that FDA future approvals just may be based on biomarkers and if you have a safe drug to target it. The global biomarker of flipped PS is a good one to have and just may not be able to be surpassed.

The successful candidate will join our team and work to identify and profile biomarkers in preclinical models and implement diagnostic and pharmacodynamic assays in clinical trials of novel therapeutics.

http://www.gene.com/careers/detail/00435291/Sr-Research-Associate-Oe-Pharmacodynamic-Biomarker-Group