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Novel blood biopsy device may identify which prostate cancers will spread
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More than 161,000 men in the United States will be diagnosed with prostate cancer this year, according to SEER statistics.
The ability to determine which patients have aggressive disease — instead of a more indolent form that could be monitored over time — could improve outcomes and spare many patients from unnecessary treatment.
Researchers at Cedars-Sinai and UCLA developed a device known as the NanoVelcro Chip to identify and characterize tumor cells circulating through a patient’s blood, providing insights about how likely their cancer is to spread.
“It is far better to draw a tube of blood once per month to monitor cancer than to make patients undergo repeated surgical procedures,” Edwin Posadas, MD, medical director of the urologic oncology program and co-director of the translational oncology program at Cedars-Sinai’s Samuel Oschin Comprehensive Cancer Institute, said in a press release. “The power of this technology lies in its capacity to provide information that is equal to or even superior to traditional tumor sampling by invasive procedures.”
HemOnc Today spoke with Posadas about the technology, its potential benefits, and what questions must still be answered before the device can be employed in the clinical setting.
Question: How did the technology come about?
Answer: The technology we have been using was invented by Hsian-Rong Tseng, PhD, professor of molecular and medical pharmacology at UCLA. He is a chemist and chemical engineer involved in using nanotechnology to isolate different pieces of information from the bloodstream. Part of the original development of the device was geared toward a diagnostic tool to be used around pregnancy. However, many folks in this field found that the same principals of physics and biology could be applied to isolating rare cancer-related events in the bloodstream. Leland Chung, PhD, director of our uro-oncology laboratories at Cedars-Sinai, knew him and me. In 2011, Chung suggested we needed to collaborate. For 6 years, we have been working to bring the latest ideas in chemistry, chemical engineering and nanotechnology to prostate cancer and other cancers.
Q: How does the device work?
A: Since the 1970s, scientists hypothesized that there are cells from cancerous tumors that are shed into the bloodstream or circulatory system from the original site of the malignancy. The problem is that cancer cells in circulation — now called circulating tumor cells — is the proverbial ‘needle in a haystack.’ It is a one-in-a-million type of cell. There has long been a desire to use blood to diagnose and monitor cancer and, as nanotechnology evolved, there arose an interest in developing tools for pulling these rare events out of the bloodstream. This assay combines a nanotechnology surface with a microfluidic mixing system. The device is as a small as a quarter. The blood runs through about 12 different baffles, the purpose of which are to push cells in the blood against the NanoVelcro Chip. The chip’s surface is covered in nanometer-sized silicon wires that are coated with a predesignated trap substance. As the cells are flowed through the mixer and bounce up and down on the surface, these coated nanowires interact with small nanostructured folds on the cancer cell so proteins that stick to the surface interact with trap substances. The two surfaces form a tight bond that looks like common Velcro at the molecular level. We are able to adjust what is present on the surface of the NanoVelcro Chip to refine what types of cells the device will pull out from circulation. This is very important because we are trying to identify the proverbial ‘needle in a haystack’. Even if we were to throw the entire ‘haystack’ over this device and we have a very specific capture setup, it is not difficult to capture the needle.
Q: What challenges have you encountered with the technology?
A: We may have some incorrect or nonspecific cells that are captured, just by the physical nature of these devices. We double-check what we capture by putting a second layer of antibodies onto captured cells to further identify them. Although this is helpful, we have found that we require a human factor. We need a well-trained pathologist to look at those cells and tell us whether the putative captured object is a cancer cell. With the combination of cutting-edge mechanics, as well as classical medicine and biology, we have been able to use this tool quite effectively.
Q: What must be confirmed before the device is adopted in the clinic?
A: The actual functional characteristics of the first-generation NanoVelcro (capture) platform have been well studied. In fact, the first-generation device is undergoing review for 510(k) clearance with the FDA. This first-generation device is geared toward capturing and counting the cells and is just the tip of the iceberg with what this nanotechnology can do. Our vision has moved forward. Although enumeration is important, studying these cells will open a new world of possibilities. This may allow us to treat the blood in the same fashion as a needle or surgical biopsy of a patient’s tumor, which could revolutionize personalized medicine. There is huge demand from the NCI, patients, payers and clinicians for ways to use the growing armamentarium of tools in oncology and cancer biology in a smarter fashion. We believe we must better match patients and their cancers to their treatments. ... Some cancers, including prostate cancer, lack molecular descriptors. Our field is hindered by the absence of a molecular signature and nomenclature. We speak of Gleason Scores referring to cell and gland shapes that we see under a microscope. There is no molecular annotation, but this will come in the near future. As a field, we must be prepared for this and demonstrate its value to the field of medicine by improving outcomes for men with different molecular subtypes of prostate cancer. The hope is that these annotations will direct patients toward therapy. The goal is to maximize benefit and minimize harm.
Q: What makes this device unique?
A: We are aware that using historical material probably is not the most accurate way to characterize a tumor. If a man who [underwent surgery for] prostate cancer 10 years ago comes into my clinic today because his prostate cancer has come back and he is no longer responding to hormone therapy or other treatment, this cancer is very different than what existed in his body before. It has evolved over time. This is the problem with which we wrestle in cancer. Being able to address this head-on is important because we still cannot predict how cancers mutate over time. Therefore, having contemporary samples becomes terribly important to understand these changes. The patient undergoes a biopsy to determine the new nature of the disease, and this is useful in many cancers. However, this process is repeated as the cancer changes, exposing the patient to harm each time an invasive procedure is needed to sample tumor. Moreover, cancers are highly heterogeneous, so sampling one site may not provide a physician with all the needed molecular information.
Q: Can you describe the potential impact on patients?
A: Certain diseases pose unique problems because of their clinical behavior. For example, prostate cancer spreads to bone. If you were to tell a man that you must sample his bone once a month for the next 5 to 6 years, he likely will not respond to the request favorably. At times, we must use a drill to obtain bone samples given the osteoblastic nature of these tumors. If I can do the same thing with a blood test and monitor the molecular biology as the patient is being treated, we will reshape the face of cancer medicine.
Q: How likely is it that this device could work for m alignancies other than prostate cancer?
A: It absolutely will. We have used prostate cancer as a model because it has a particular problem in the absence of repeated contemporary biopsies. The idea of having an invasive procedure done several times a year is not pleasant. For example, patients with leukemia are accustomed to having surveillance with bone marrow biopsy. Imagine taking these samples four or more times per year. You have only four time points to describe a cancer that is capable of rapid evolution. In advanced disease, a malignancy can alter its behavior on the order of weeks. However, with a blood test, one creates the possibility of creating a detailed time line of molecular changes capturing and describing the dynamic biology of cancer. I see this as a huge benefit across different cancers. We would have to make small adjustments in the approach to meet those cancers, but the amount of information we have already unmasked allows our platform to be used in prostate, kidney and pancreatic cancers, melanoma and other malignancies.
Q: Is there anything else that you would like to mention?
A: Many people will hear about these technologies and think it will take as long as a decade to see this become available. However, we really are not far off. These changes are happening now. A number of platforms are maturing. Much of these have been the result from brilliant foresight and support from the NIH and the NCI, such as the Alliance for Nanotechnology in Cancer and the Innovative Molecular Analysis Technologies Program. The push from the NIH and NCI is to bring all of these emerging technologies to the clinic within the next 2 years. – by Jennifer Southall
For more information:
Edwin Posadas, MD, can be reached at Cedars-Sinai Medical Center, 8700 Beverly Blvd., West Hollywood, CA 90048; email: edwin.posadas@cshs.org.
Disclosure: Posadas reports no relevant financial disclosures.