The University of Texas MD Anderson Cancer Center announced last week that it has received $20 million from businessman Ross Perot to fund two initiatives – the Institute for Personalized Cancer Therapy and the Center for Targeted Therapy.
The donation will fund research at the centers exploring more effective drug treatments for cancer patients, including investigations into protein pathway-directed therapies, Stanley Hamilton, co-director of the IPCT, told ProteoMonitor.
The CTT, which is part of the Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer, focuses on coordinating the various stages of drug discovery, from the identification and validation of new targets through to the development of therapeutic agents targeting them.
The IPCT is a multi-center initiative that aims to bring a pathway-based approach to MD Anderson's cancer research. Planning of the program began two years ago in response to the growing emphasis on the development of pathway-directed therapies in the pharmaceutical industry and the realization that cancers might be better grouped according to pathway activation rather than site of origin.
"[MD Anderson] is organized into multi-disciplinary care centers that are disease-site specific," Hamilton said. So, what was happening was with the different [disease-site specific] groups, often the targets were the same, and often the agents that were targeting them were a similar class of drug, or sometimes even the same drug."
"The paradigm of, 'This is breast cancer, so we use this drug, and this is colon cancer, so we use this other drug,' is coming under scrutiny because many of the same pathways are aberrant in different types of tumors," he said. "We need to get away from thinking about breast cancer, colon cancer, brain cancer, to thinking about [cancers] that are AKT pathway-related, for instance, particularly since the agents that are coming in the pharmaceutical pipelines are directed at those pathways."
This change in thinking has led MD Anderson, through the IPCT, to launch a number of studies investigating drugs targeting various cancer-linked protein-signaling pathways. According to Hamilton, researchers are examining the "whole spectrum – MET, PI3K, AKT, MTOR," looking at "the whole range of inhibitors that are in the pipeline from pharmaceutical companies."
Such pathway-directed research has become increasingly common in cancer studies. This month, Merck scientists published a paper detailing the effects of three investigational cancer drugs on phosphorylation levels of proteins involved in the PI3K pathway (PM 08/06/2010). And researchers like George Mason University's Lance Liotta and Emanuel Petricoin are conducting similar studies across a range of cancers including those of the lung, breast, prostate, kidney, and brain (PM 08/13/2010).
As Petricoin told ProteoMonitor earlier this month, "What we're learning is that cancer is a pathway disease, not a site-of-origin disease."
"A lot of people have had this idea," Hamilton said. It's really become widely recognized that the different pathways are often activated or inactivated by different mechanisms or in different tumors, but the end result may be the same. I think it remains to be seen on the basis of clinical trials whether that is in fact true, and that's why we want to do the studies,"
The first study to emerge from the IPCT was the BATTLE lung cancer trial, which was presented in April at the American Association for Cancer Research annual meeting. The first clinical trial to perform molecular analysis of lung tumors, the study examined over 300 patient tumors for the presence of 11 different biomarkers, including gene mutations and proteins, and assigned subjects to one of four different treatment arms based on that analysis.
Additional studies like the BATTLE trial are on the way, Hamilton said.
"We've got a whole series of them. It's probably a couple dozen subsequent trials like that," he said, citing three in development for lung cancer and two others in development looking at pathways across a variety of organ sites.
"The common theme is the acquisition of tumor tissue for the evaluation of the presence of the targets, and then to drive the selection of therapy based on what targets are present in the tumors," he said.
The donation, he said, will be used to broadly support this work, funding "the purchase of equipment, the development of CLIA-based assays, supporting research nurses, data management, bioinformatics – it really depends on what the individual investigator proposing the trial needs to get the work done."
Perot has been a longtime donor to MD Anderson, in 2004 establishing the center's Norman Brinker Award for Research Excellence. In addition to the Perot money, the IPCT has received funding from several other philanthropic organizations, as well as "a fair amount of internal money" from MD Anderson itself, Hamilton said.