For decades the standard approach to cancer treatment typically has been some combination of surgery, chemotherapy and radiation therapy. Chemotherapeutic agents routinely produced unwanted side effects as not only cancer cells but also some populations of healthy cells were destroyed. Highly targeted therapies to fight specific forms of cancer have been emerging over the last several years, but a recent study suggests a new approach based on nanoparticles and RNA interference might be on the horizon.
Traditional Therapy Approaches to Cancer Treatment
Since the advent of the standard array of medical interventions over the last half of the 20th century, a diagnosis of cancer meant that the potential treatment approaches were defined upon the characteristics of the type of cancer identified. This included whether the tumor was locally contained, how malignant the cells appeared in the microscope, and where the tumor was located. If at all feasible, an isolated tumor could be removed by surgery. However, if surgery could only remove part of the tumor or if a surgical approach was not possible, or if signs indicated that the tumor cells might have spread, chemotherapy and radiation therapy were utilized.
Since the 1960s, the number of treatment approaches available for the cancer patient and their treating surgeon or oncologist has steadily improved. And the important benefits of early diagnosis have also become clearly established. Unfortunately, many of the drugs used to fight cancer have significant side effects. And while the drugs available to treat side effects such as vomiting caused by chemotherapy have steadily improved (e.g. Zofran), the hope remains that highly targeted therapies will be able to eradicate cancer cells while limiting the number of unpleasant and sometimes life-threatening side effects.
Targeted Therapies Continue to Emerge
One of the problems associated with most chemotherapy drugs is that they lack selectivity; that is, they are meant to kill any rapidly dividing cell. This is a good property as it relates to most cancer cells but not so good when considering that normal cells present in the lining of the intestines or in the mouth or in the bloodstream for example can also be killed by this approach.
The discovery of particular molecular and biochemical characteristics of specific tumor cells has allowed for the development of much more targeted treatments. Recent approaches to targeted tumor therapies include specialized enzyme inhibitors such as Gleevec (Imatinib) and antibodies targeting tumor proteins such as Herceptin (Trastuzumab). Approaches like these have met with some significant measure of success, and in many cases have been able to considerably limit side effects.
Targeting Gene Expression in Tumors
An evolving approach to the treatment of tumors is to interfere with the expression of specific genes inside the tumor cells using RNA interference. In this process, engineered nucleic acids, once inside the cell, shut off the synthesis of a specifically targeted protein by interfering with the translation of its messenger RNA.
The results of a new study show that tumor cell gene expression can be inhibited by using nanoparticles to deliver a specific type of RNA interference reagent (small, interfering RNA or siRNA) to solid tumors in patients with melanoma (Davis). Intravenously administering nanoparticles covered with siRNA to interfere with the production of an enzyme important for the growth of melanoma tumors, the researchers found that the nanoparticles accumulated inside of tumor cells. More importantly, the researchers also found that the expression of the particular enzyme they were targeting, the M2 subunit of ribonucleotide reductase, was significantly reduced. While not the first study to utilize nanoparticles or siRNA, this is the first study to show that the delivered siRNA reagent specifically interfered with gene expression inside of a tumor.
The results of this new study indicate that the delivery of RNA interference reagents to tumor cells using nanoparticles is technically possible but much work remains. Nonetheless, these data suggest that this approach could be used for other types of tumors in the future raising the hope of exquisitely targeted therapeutic agents with the ability to interfere specifically with tumor cell growth.
Davis ME, Zuckerman JE, Choi CH, Seligson D, Tolcher A, Alabi CA, Yen Y, Heidel JD, Ribas A. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature. 2010 Mar 21. [Epub ahead of print] PubMed PMID: 20305636.