Nanotechnology sheds light on cancer stem cell therapy
A new nanotechnology breakthrough is helping scientists and oncologists evaluate why a certain subset of early-stage cancer cells, called cancer stem cells (CSC), are resistant to many front-line chemotherapy drugs. It's also offering a faster and cheaper methodology for the development of more effective therapeutics.
Led by Jackie Y. Ying, a professor and executive director at the Institute of Bioengineering and Nanotechnology (IBN), a team of researchers developed a miniature droplet analytic array -- a flat, rectangular piece of glass -- with a series of spots, each 2 millimeters in diameter. Each spot is capable of screening 500 cells, a huge reduction in sample volume over traditional screening arrays, which often require 2,500-5,000 cells for a viable analysis. Utilizing the nanoarray, IBN researchers analyzed stem cells from liver, breast and colon cancer cells and found poor efficacy with traditional chemotherapy drugs, which normally kill later stage cells in all of these tumor types.
Follow-up experiments in mice validated the findings. CSCs and non-CSCs from liver tumors were implanted in mice at the same time. Six weeks later, only the mice with CSCs developed tumors, which also showed blood vessel formation when extracted, substantiating the self-renewal properties of CSCs.
The IBN experiments represent an enormous step on two forefronts: cost and efficiency. CSCs represent less than one percent of all cancer tumor cells. With standard arrays needing thousands of cells for an analysis, simply growing enough cells for an experiment represents an enormous challenge. Secondly, because of its smaller properties and cell analysis features, the droplet arrays will save labs thousands of dollars in reagent and specimen costs, especially due to the chip’s compatibility with existing laboratory equipment. Finally, Dr. Ying hopes that the accuracy and speed of the droplet array may help to replace many unnecessary animal models for drug toxicity and efficacy.
But, what are cancer stem cells and why are they such a focal point at the forefront of cancer treatment? Like their normal human tissue counterparts, cancer stem cells are an early-stage progenitor cell, capable of differentiating and developing into various lineages and cell types, most notably those found in a particular type of malignancy. The CSC hypothesis suggests that the malignancies associated with cancer originate from a small population of stem-like, tumor-initiating cells. When enough genetic modifications affect these subsets of cells (radiation, exposure to carcinogens, certain genetic mutations), they either become tumor-initiating cells or expand to drive the growth of a tumor. This hypothesis was most expansively shown to date in various leukemias and their hematopoietic stem cell progenitors (HSCs). Catapulted by this research, CSCs have also been isolated in brain, breast, colon, ovarian, pancreatic, prostate, melanoma and multiple myeloma cancers. Many researchers are convinced that the key to effective cancer therapy of the future will be to target this progeny of cells in patient populations through the use of stem cell biomarkers in concert with highly-specific CSC drugs.
Because current therapies aggressively target only the most rapidly-dividing cells in a tumor, many scientists theorize that they are not properly targeting the subpopulation of CSCs, which stay alive, and simply give rise to more tumors and relapses. A major challenge, however, has been the isolation and identification of cancer-specific stem cells from normal stem cells. In fact, until very recently, many scientists have even doubted the drug resistance properties of CSCs, partially because they have been so difficult to quantify and study in depth, rendering the latest advance even more impressive and significant.
Scientists have channeled the power of nanotechnology to develop a multitude of applications and benefits across society. Some of these include nanoengineered materials present in over 800 everyday commercial products (including sports equipment, armor, the food industry and machinery), more energy efficient electronics and IT, sustainable energy and environmental solutions. The most promising area is health and science research. Gold nanoparticles have been used to detect everything from Alzheimer’s to cancer. Scientists have developed nanowire AFM imaging techniques sensitive enough to detect singular molecular events and signals in vivo. Quantum dots provide 1,000 times the resolution of traditional biological imaging such as MRIs, with vastly more information for doctors. The list goes on and on.
This latest discovery allows scientist to do the once unthinkable: move an entire lab onto a microscale chip. What once would have taken years will now take weeks. And it is entirely possible that each subtype of cancer, with its own complex stem cell progenitor and propagation pathway, will not only be elucidated but also matched with an appropriate, effective drug therapy.