Lance Liotta, MD, and Emanuel Petricoin, III, professors of life sciences and co-directors of George Mason University's Center for Applied Proteomics and Molecular Medicine (CAPMM), are pioneers in the field of patient-tailored research and personalized medicine. The two are studying biomarkers or 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, MD, medical director of cancer services at Inova Health System, and Alexander I. Spira, MD, director of Fairfax Northern Virginia Haematology Oncology Research Programme, to treat patients with late-stage colorectal cancer, a fatal cancer that starts in either the colon or the rectum.
The three-year trial will accommodate up to 50 men and women who have late-stage colorectal cancer that has spread to the liver. Striking more than 150.000 men and women each year in the United States, colorectal cancer is the nation's third most commonly diagnosed cancer and third leading cause of cancer death according to the American Cancer Society.
"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 tumour based on its unique protein make-up. 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 towards the individuality of a patient's disease state. This clinical trial is the first step toward doing that", stated Kirstin Edmiston.
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 gastro-intestinal tumours. Gleevec targets disease pathways in tumour cells that previous CAPMM research revealed were among those found in typically fatal liver metastasis in colorectal cancer patients.
Because the primary tumours 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 tumours or metastatic lesions that appear when the disease spreads to the liver, causing death through destruction of that organ.
Using a new drug target mapping technology called "reverse phase protein micro-array" that was developed by CAPMM's scientists, the researchers will sample these lesions and 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 this particular patient before it is even administered.
By monitoring the drug target activity in trial participants' tumours and basing their treatment on those characteristics, the researchers are hopeful that this clinical trial will lead to more effective and individualized treatment for patients who suffer 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", stated Emanuel Petricoin. "Until now, the most cutting edge clinical trials utilize genomic profiling of the tumour 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 patient's tumour - just technologically being able to do this in a real clinical trial is a first."
Financial support for the study is being provided by Novartis, which developed and manufactures Gleevec.
Inova Health System is a not-for-profit health care system based in Northern Virginia that consists of hospitals and other health services, including emergency- and urgent-care centres, home care, nursing homes, mental health and blood donor services, and wellness classes. Governed by a voluntary board of community members, Inova's mission is to improve the health of the diverse community it serves through excellence in patient care, education and research.
Fairfax Northern Virginia Haematology Oncology (FNVHO) is northern Virginia's premier oncology and haematology practice of board certified physicians. The practice has 33 physician experts on cancer, blood disorders and stem cell transplantation in seven locations across northern Virginia. Comprehensive practice services include collaborative nursing, financial counseling and access to cutting-edge clinical trials through affiliations with U.S. Oncology, the National Cancer Institute and many other co-operative groups.
Named the number 1 national university to watch in the 2009 rankings of U.S. News & World Report, George Mason University is an innovative, entrepreneurial institution with global distinction in a range of academic fields. Located in Northern Virginia near Washington, D.C., Mason provides students access to diverse cultural experiences and the most sought-after internships and employers in the country. Mason offers strong undergraduate and graduate degree programmes in engineering and information technology, organisational psychology, health care and visual and performing arts. With Mason professors conducting groundbreaking research in areas such as climate change, public policy and the biosciences, George Mason University is an example of the modern, public university.