Pharmaceutical Technology Europe - April 2010 - (Page 11)

Personalising cancer therapy We have recently launched a novel personalised therapy clinical trial to treat patients with late-stage colorectal cancer at George Mason University’s Center for Applied Proteomics and Molecular Medicine (CAPMM). This is one of the most cutting-edge personalised therapy clinical trials in the world for several reasons including: • it uses protein information rather than genomic information to guide therapy • the activation state of the protein, not its total amount, is used to guide therapy • therapy is tailored to the molecular signature of the metastatic lesion rather than the primary tumour • the input to the analysis is tumour cells isolated from the metastatic lesion itself using a technique we invented called laser capture microdissection (LCM) • it uses a novel protein microarray, the reverse phase array (RPMA), to map the activation state of the protein network. In particular, the trial will be testing Novartis’s Gleevec, which is FDA-approved for chronic myelogenous leukemia and gastrointestinal tumours. According to research conducted at CAPMM, Gleevec targets disease pathways in tumour cells that are among those found in typically fatal liver metastasis in colorectal cancer patients. For our, trial, a patient’s metastasis is sampled using a needle biopsy and the pure tumour cells are isolated using LCM. They are then solubilised and analysed with the reverse phase protein microarray, and the activation states of the Gleevec drug targets (ckit, cabl and PDGFr) are assessed. Gleevec is then given to patients with highly activated signatures while patients whose network is not activated are given the standard care therapy. Gleevec would not normally have been considered for treatment in these cases. In the new paradigm of personalised therapy, however, the site of the cancer does not matter because it is the molecular signature that drives selection — true personalised therapy. We hope to have results on a statistically significant number of patients by the end of the year. techniques, the technology can achieve the sensitivities of measuring the level of a protein in less then a 1-cell equivalent. With RPMA, we wanted to develop a technology that could directly measure what we really want to see: the activity of the protein drug target itself in patients’ tumours. PTE Reverse phase protein microarray technology Key to the trial is the RPMA drug target mapping technology. Because you don’t know which pathways are activated and driving tumour growth, you need to measure many things to find the correct culprits — RPMA can do this using only a tiny specimen. RPMA involves printing nanolitres of cellular lysates of cells and body fluids. Using sophisticated amplification Based on contributions by Dr Emanuel Petricoin and Dr Lance Liotta, Professors of Life Sciences and Co-Directors at the Center for Applied Proteomics and Molecular Medicine, George Mason University (VA, USA). To read the full version of this article, go to www.pharmtech. com/georgemason www.capmm.gmu.edu/EN/ 1 CONTENTS 9 THE HUMAN GENOME 2 INTRODUCTION 11 CANCER THERAPY UPDATE 5 MORE THAN SCIENCE NEEDED 14 MANUFACTURING CHALLENGES 7 FUTURE SNP MARKET 16 TOP TECHNOLOGIES http://www.pharmtech.com/georgemason http://www.pharmtech.com/georgemason http://capmm.gmu.edu/EN/

Table of Contents for the Digital Edition of Pharmaceutical Technology Europe - April 2010

Pharmaceutical Technology Europe - April 2010
Table of Contents
Why Personalised Medicine Business Models will Require Long-Term Strategies and Great Flexibility in Order to be Successful
Science Alone Will Not Lead to Better Medicines
The Current and Future Market for SNPs
The Hype, Hope and Reality of Pharmacogenetic Tests
Unraveling the Human Genome
Progress in Molecular Diagnostics
Personalising Cancer Therapy
T Cells for Patient-Specific Cancer Treatments
Future Research Strategies for Glucocorticoid Therapy
Overcoming Manufacturing and Financial Challenges of Personalised Cell Therapies
Public-Private Partnerships Prosper
Eight Latest Technologies Showcased

Pharmaceutical Technology Europe - April 2010