Yet another reason the FDA needs to modernize for the 21st century (Re: colon cancer)
Mason Researchers Launch Innovative Clinical Trial for Colorectal Cancer
George Mason University Published January 19, 2010 By Marjorie Musick
Imagine if treatments for disease could be based not on patients’ diagnoses, but instead on the characteristics of their tissue. By identifying and decoding the cryptic messages hidden deep inside the human proteome, scientists and physicians who study personalized medicine are seeking more effective treatments and disease management for patients.
Lance Liotta and Emanuel Petricoin III, professors of life sciences and co-directors of Mason’s Center for Applied Proteomics and Molecular Medicine (CAPMM), are pioneers in the field of patient-tailored research and personalized medicine. The two study biomarkers (indicators of disease in tissue and bodily fluids) related to cancer, heart disease, liver disease and obesity.
They recently launched a unique clinical trial in partnership with oncologists and co-principal investigators Kirstin Edmiston, medical director of cancer services at Inova Health System, and Alexander I. Spira, director of Fairfax Northern Virginia Hematology Oncology Research Program, to treat patients with late-stage colorectal cancer, a fatal cancer that starts in either the colon or the rectum.
Striking more than 150,000 American men and women each year, colorectal cancer is the nation’s third most commonly diagnosed cancer and third leading cause of cancer death, according to the American Cancer Society.
The three-year trial will accommodate up to 50 men and women who have late-stage colorectal cancer that has spread to the liver.
“Traditionally, all colon cancers have been lumped together and given similar treatments. The novelty about this is that we can, in a very minimally invasive way, start to treat the metastatic tumor based on its unique protein makeup,” says Edmiston.
“If we’re going to be successful in treating the metastatic disease, which is what kills people, then we need to focus on using therapies targeted toward the individuality of a patient’s disease state. This clinical trial is the first step toward doing that.”
Trial participants will be treated with standard metastatic colon cancer therapy and will test the addition of Gleevec, a medicine that is typically prescribed for certain forms of leukemia and gastrointestinal tumors. Gleevec targets disease pathways in tumor cells that previous CAPMM research revealed were among those found in typically fatal liver metastasis in colorectal cancer patients.
Because the primary tumors in the colon are removed in most colorectal cancer patients as soon as they are diagnosed, this study will focus on treating the often fatal secondary tumors or metastatic lesions that appear when the disease spreads to the liver, causing death through destruction of that organ.
To sample these lesions, CAPMM’s scientists developed a new drug target mapping technology called “reverse phase protein microarray.” This allows the researchers to create a unique molecular profile or “fingerprint” that shows which protein pathways or drug targets are activated in the lesion. This process will allow the researchers to determine whether specific drugs such as Gleevec might be an effective treatment for a particular patient before it is even administered.
By monitoring the drug target activity in trial participants’ tumors and basing their treatment on those characteristics, the researchers are hopeful that the clinical trial will lead to more effective and individualized treatment for patients suffering from this devastating disease.
“The exciting aspect of this trial is that an established drug is being considered for a new indication, and that’s one of the promises of personalized therapy — that a patient’s molecular portrait would be considered as the rationale for choice of therapy rather than based on the site or the kind of cancer alone,” says Petricoin.
“Until now, the most cutting-edge clinical trials utilize genomic profiling of the tumor to select patients. This is the first trial that uses a direct proteomic approach that maps the drug target activation networks that are in use in each patients’ tumor — just technologically being able to do this in a real clinical trial is a first.”
Patients interested in participating in the clinical trial should contact Stacey Banks, Inova’s clinical research coordinator, at 703-776-3565.
Financial support for the study is being provided by Novartis, which developed and manufactures Gleevec.