Circulating Tumor Cells and Early Diagnosis

A recent report describing a novel application of the cell search technology developed by Veridex, LLC (a subsidiary of Johnson & Johnson) may provide an extremely sensitive tool for the early detection of cancer. Four major cancer centers in the United States will conduct an analysis to determine the accuracy of this method for early diagnosis.

Over recent years, it has been recognized that cancer patients circulate small numbers of tumor cells in their blood. Using microbead technology, these tumor cells can be isolated from the blood stream and characterized. The original application of the technology was a prognostic marker by which patients with breast, colorectal or prostate cancers and high levels of circulating tumor cells, fell in the “high-risk” groups. I have been highly supportive of the application of this technology and have applied it extensively for patients with prostate and breast cancers.

The more recent iteration of this technique will allow investigators to not only identify but also characterize the isolated tumor cells. This provides an exciting new opportunity for early diagnosis.

As we speculate on the ramifications of this discovery, certain questions are raised. The most immediate being: What to do with the data? It has previously been suggested that many cancers arise 20 or 30 years before they are clinically detected. Malignant populations measuring in the hundreds of thousands, millions or even hundreds of millions, may still lie below the radar screen of modern diagnostic tools. If we have the capacity to identify patients 10 or 20 years before their cancers can be clinically detected, would we then begin therapy decades before clinical disease arises? If so, what treatments will we administer? Will the early detection of cancer cells be associated with the further characterization of tumors, such that targeted agents can be utilized to eliminate these clones at their earliest inception?

We will watch the development of these clinical studies with great interest. It will be even more interesting to see how we answer the questions that arise.

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

2 Responses to Circulating Tumor Cells and Early Diagnosis

  1. Eileen Campbell says:

    Dr. Nagourney, what are the most recent findings in treatment of pancreatic cancer? My friend is being treated with Xeloda, concurrently with radiation and chemo and will be treated with gemzar after surgery. The tumor is large and is sitting on a major artery. the hope is that the radiation will shrink or move the tumor away from the artery so that surgery can be done.

    Could you please provide me any information regarding the latest treatment for his cancer? It has not metasticized except for one lymph node in the pancreas area. Thank you.
    Eileen Campbell

    • Dear Eileen:

      As you are aware, pancreatic cancer is among the more difficult cancers to cure. The median survivals are unfavorable and many patients suffer pain and weight loss. Despite the gravity of the diagnosis, we have seen some truly remarkable responses. The therapy that you outlined is a very appropriate and widely used approach. The addition of Xeloda provides “radiopotentiation” for the radiation and the use of of Gemcitabine in the adjuvant setting has provided unexpectedly good improvements in survival. As there is no uniformly effective combination, we have been very interested to apply directed combinations, using our platform to select drugs to combine with radiation and/or surgery. One such patient has just had a re-exploration for what may be a new primary 7 and 1/2 years after I first treated him for his “inoperable” pancreatic cancer. Our longest living patient with metastatic diseae went 11 years and was actually the subject of an article in Scientific American in July of 1998. He was one of our very first “assay-directed” patients. To put this in context, pancreatic cancers are actually quite different one from the next. While the addtion of Erlotinib to Gemcitabine may be dramatically effective in one patient, it may have no impact upon the next. While GTX ( a 3 drug combination pioneered by investigators in NY) seemed highly active in some patients, it could not improve overall survival in unselected groups. While recent reports of Gemcitabine plus Taxanes have caught the attention of many investigators,we see some patients for whom this combination is utterly ineffective in the laboratory. For these reasons, where possible, we try to study each patient’s tumor to make these decisions. Our interests extend beyond the classic cytotoxic drugs to include some of the targeted agents like the EGFr, mTOR and PI3K inhibitors all of which are slowly being incorporated into therapy If a surgery is ultimately being considered in this case, one might consider using the tumor tissue removed to help guide the post op therapy.

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