1. Eastman, Peggy

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WASHINGTON, DC-A new report from the National Cancer Policy (NCPF) of the Institute of Medicine (IOM) identifies specific ways in which nanotechnology-the science of the very small-can be useful in oncology and cancer research. Those uses encompass cancer diagnosis and monitoring, treatment and prevention, and many of these potential uses are already being studied in clinical trials. The report also pinpoints challenges and risks associated with nanotechnology in oncology.

Nanotechnology... - Click to enlarge in new windowNanotechnology

The new report is the result of an IOM workshop on nanotechnology and oncology held last year (OT, 10/25/10 issue). At that workshop, NCPF member and chair of the workshop planning committee Edward J. Benz, Jr., MD, President of Dana-Farber Cancer Institute, told OT that although nanotechnology is one of those fields that everyone agrees is very important, there are many real concerns about nanotechnology in medicine, including how to regulate therapeutically used nanoparticles that may stay in the body for a long period of time.


Recognizing nanotechnology's promise in oncology, the National Cancer Institute established the Alliance for Nanotechnology in Cancer in 2004; the goal is to encourage researchers in the field and speed the pace of discovery.


Fast Pace

That pace is already moving very fast, according to a table in the new report, which gives a partial list of more than 20 nanotechnology drugs currently in clinical trials for a host of cancers ranging from solid tumors to blood cancers.


Nanomaterials used in medicine include:


* Nanoparticles (nano-sized particles) used to target tumor and other cells for imaging or treatment.


* Nanoshells, which have a core of silica and a metallic outer layer and can be decorated with molecular probes for cancer-related compounds.


* Quantum dots, nanoparticles made from semiconductor materials that can be linked to an antibody or other molecule capable of binding to a target.


* Nanowires with diameters in the nanometer range, which are valued for their structural and electronic properties.


* Fullerenes such as "buckeyballs," which have exceptional strength and unique electrical and thermal properties.


* Micelles and liposomes, particles made from lipids.


* Dendrimers, ordered, branched polymers (each branch can be designed to have a different nanomedicine or diagnostic compound).



The report stresses that nanotechnology can be especially useful in cancer because of cancer's complexity; cancerous tumors are not only heterogeneous, but they continue to change with time. Nanotechnology can improve precision and control, emphasized workshop speaker King C. Li, MD, MBA, Professor of Radiology at Weill Cornell Medical College and holder of the MD Anderson Foundation Distinguished Chair in the Department of Radiology at Methodist Hospital in Houston.


Nanotechnology has the potential to improve the diagnosis and monitoring of cancer by enabling high-throughput detection of complex molecular signatures and enhancing imaging contrast. For example, nanochips can be used to separate out proteins in blood by size and charge, thus fostering identification of a cancer's molecular signature in an individual patient.


In imaging, magnetic iron-based nanoparticles with fluorescent tags can act as enhanced magnetic resonance (MR) contrast agents and thus be used for MR-based assays, the report notes. And clinical trials are currently under way using silica-gold nanoshells as real-time molecular probes for breast tissue that overexpresses the breast cancer biomarker HER2.


Enhance Precision

In cancer treatment, notes the IOM report, nanotechnology is likely to enhance the precision of targeting the desired cells with an anti-cancer drug, thus reducing unwanted side effects by reducing a systemic spread through the body.


Nanomedicines to treat breast or ovarian cancer encase a conventional cytotoxic drug such as paclitaxel in albumin (nab paclitaxel) or liposome nanoparticles, which do not release their contents until they reach the target cells, thus reducing damage to healthy cells.


One major benefit: the maximum tolerated dose of the drug is far higher when it is encased in a targeted nanoparticle. The report notes that studies have shown that tumor necrosis factor (TNF)-use of which has been limited by toxic reactions-can be safely administered at high doses to melanoma patients if it is contained in gold nanoparticles.


Cancer Prevention

In the field of cancer prevention, nanotechnology could be useful in delivering enough of a cancer-fighting compound to patients when those patients could not take in that compound in high enough quantities by ordinary means. For example, the report cites epigallocatechin-3-gallate (EGCG), a compound found in green tea that has cancer-fighting activities but poor oral absorption.


A research laboratory at the University of Wisconsin has created a nanoparticle that can deliver high doses of EGCG, and is studying it in an animal model of prostate cancer. In the animal model, the nanoparticle-enclosed EGCG induced programmed cell death, inhibited the formation of new blood vessels, and decreased tumor volume.


Speakers at the 2010 workshop had emphasized that much work remains to be done to improve the design and development of nanomedicines, which is where research comes in. Thus the IOM report notes that nanomedicines for oncology will be improved by an increased understanding of basic biology and the pathogenesis of cancer. Particularly important, the report notes, is increasing knowledge on what constitutes a precancerous lesion, and how to detect populations at risk that might be candidates for prevention studies using nanomedicines designed to lower cancer risk.


Safety Issues

The IOM report explores in detail safety issues related to nanotechnology in oncology. At this time, the long-term toxicities of nanoparticles used for medical purposes remain unknown.


Nanostructures can enter the cells of organs and reside in them for an unknown period of time before moving to other organs or being excreted, with unknown effects. Some IOM workshop participants stressed the need for collaboration among regulatory agencies, including the Food and Drug Administration and the Environmental Protection Agency.


"One of the biggest challenges for us is to turn the unknown to the known so we don't have a lot of unrealistic fears," said Steven K. Libutti, MD, Director of the Montefiore-Einstein Center for Cancer Care, Associate Director of the Albert Einstein Cancer Center, and Professor and Vice-Chairman of Surgery and Professor of Genetics.


Dr. Libutti pointed out in the report that the general public has natural fears about nanotechnology, about which there are many unknowns, fed by a predilection for watching science fiction movies. The report stresses that the public needs more and better education on what nanotechnology is, including what nanotoxicity means in the environment or in food, versus what it means in medicine.


The new IOM report reflects workshop participants' conclusion that knowledge fights fear. Thus increasing knowledge on biodistribution, metabolism, excretion, and degradation of nanomaterials will help lead to demystification of this new field.


For those nanoparticles that are not metabolized or excreted, studies will need to be done to track their long-term effects in the body, if any. If some nanoparticles are hard to track in vivo, as appears to be the case, new ways of tracking them will have to be identified.


In nanotechnology as in other therapies used in oncology, the key will be risk/benefit analysis and management, the IOM report states.