A new assay will give clinicians their first practical laboratory test to guide the use of new-generation drugs that can kill cancer cells by simply cutting off their blood supply, according to an article published in the Journal of Internal Medicine this week.
The test, called the MicroVessel Vascular assay was developed, almost by accident, by Larry Weisenthal, MD, PhD, a medical oncologist and founder of Weisenthal Cancer Group (Huntington Beach, California).
"It's more of a discovery instead of an invention," Weisenthal told Diagnostics & Imaging Week. "Throughout my career I have read more than 500,000 microscope slides containing tumor biopsies from more than 10,000 human patients. But in 2006 I received an interesting specimen and saw something very different."
Weisenthal would see the tumor cells of a patients suffering from a form of pancreatic cancer that struck Apple CEO Steve Jobs.
What he found was that the tumor cells contain endothelial cells which are present even when these have been dissociated to allow for cell culturing. These Endothelial cells form blood vessels through a process called angiogenesis. These blood vessels, in the form of microcapillaries, carry oxygen and nutrients to tumor cells and allow for removal of waste products.
It has been shown that in order for a cancer cell to live it must be separated by no more than two or three cell layers from a blood supply.
In an excerpt from his findings Weisenthal wrote that "a promising goal for cancer treatment is to impede the formation of microcapillaries. There has been a rush among pharmaceutical companies to develop a new class of anti-cancer drugs called angiogenesis inhibitors. Currently, most of these drugs target a molecule called VEGF (vascular endothelial growth factor)."
As the name implies, endothelial cells seem to require VEGF in order to live, multiply and form capillaries. Drugs that inhibit EGF expression or interfere with its action are widely-regarded as being among the most promising of cancer treatments to come along in decades.
MVV is drug-specific and can determine specifically if Avastin, Sutent, Nexavar or a different angiogenesis-inhibiting drug is indicated, on a patient-by-patient basis, based upon demonstrated in vitro drug activity against each patient's actual endothelial cells.
Contrast that with molecular methods, which test only fixed, dead cells, never exposed to angiognesis inhibiting drugs and which identify only a potential and non-specific VEGF endothelial cell dependency.
MVV identifies active combinations of specific angiogenesis-inhibiting drugs and neoplastic agents. It can discriminate antineoplastic effect from anti-angiogenesis effect in mixed-cell populations.
"What we can do for the first time is take real human cancer and find if combination drugs work in killing it," he said.
He noted that the test could even offer results on different combinations that would go so far as to be alternatives to the popular cancer treatment drug Avastin, manufactured by Genentech (South San Francisco, California). "Avastin is bankrupting our healthcare system," Wiesenthal said. "It costs $10,000 a month to use it." In 2007 the drug had sales topping $2.2 billion in the U.S.
He said there have been no clinical trials to date in which patient treatments have been selected systematically on the basis of information derived from the MVV assay. But for more than a year he has been reporting MVV assay results to select physician collaborators. In some cases physicians have weighed the test results, along with other clinical factors, in designing individualized patient treatments. Patient outcomes results have been reported to him and in many cases there has been a positive correlation between in vitro and in vivo drug activity.
Weisenthal said he plans to open recruitment to a clinical trial, to be sponsored largely by patients who enter the trial. No sponsorship has been sought from any drug company or government agency.
He said that he would like to see the test become available to patients worldwide through service agreements with larger laboratory companies or with a biotechnology company which might develop a testing kit for sale to hospitals and laboratories. He also would like to license the test to pharmaceutical companies for use in new drug development.
"We're just a small lab here," Weisenthal said. "We don't have the capacity to run large amounts of these tests."
He added that "the long-awaited magic-bullet cure for cancer hasn't materialized. Now we're thinking more in terms of long-term control such as is the case with high blood pressure or diabetes. The way to make that happen sooner is to use our current ammunition more affectively."
Weisenthal Cancer Group is a privately held commercial cancer testing laboratory and research facility. The company was founded in 1992.