On Jan. 28, 2004, NCI convened a symposium to explore how nanotechnology can foster strategies to target cancer. Although several specific technologies were discussed, the goals of the meeting were to identify state-of-the-art approaches for advancing cancer imaging through nanotechnology, as well as pinpointing barriers to accelerating progress of this field.
Nanotechnology refers to the interactions of cellular and molecular components and engineered materials - typically clusters of atoms, molecules, and molecular fragments - with dimensions that are normally, though not exclusively, smaller than 100 nanometers.
Attending the symposium were experts representing 35 cancer centers, engineering programs, and companies. NCI Director Dr. Andrew C. von Eschenbach spoke about creating NCI's Cancer Nanotechnology Plan for developing platforms, standards, and innovative research and training for this emerging field.
The meeting, led by Dr. Lee Hartwell, director of the Fred Hutchinson Cancer Research Center, Dr. Mauro Ferrari, of Ohio State University, and NCI's Drs. Daniel Sullivan and Peter Choyke, featured methods to develop nanoscale contrast agents for multimodal imaging techniques, including optical, nuclear, ultrasonographic, and magnetic resonance techniques. Experts emphasized a need to establish standardized testing methods to enable comparisons of the applicability of various nanoparticles to different imaging tasks, such as molecular tumor cell recognition.
Participants identified the barrier of the lack of identified targeting molecules, which would provide better specificity for any imaging agent. Researchers also pointed to the lack of an established commercialization pathway for clinically applied cancer imaging agents as a major obstacle.
NCI-supported investigators have created nanotechnology platforms that hold promise for simultaneously diagnosing and treating cancer. Some of the fruits of these projects are in preclinical studies designed to lead to human clinical trials. NCI is also developing programs that apply nanotechnologies as tools for systematic interrogation of cellular and molecular processes of basic cancer biology.
People with inflammatory bowel disease tend to have an increased risk for colon cancer. Conversely, research last summer showed that people who take nonsteroidal anti-inflammatory drugs have a decreased risk for the disease.
A new study in the Feb. 4, 2004, Journal of the American Medical Association by Dr. Thomas P. Erlinger and colleagues at the Johns Hopkins Medical Institutions shows that persons with elevated levels of C-reactive protein (CRP) were more than twice as likely to develop colorectal cancer. The investigators followed nearly 23,000 adults for up to 11 years and found that those who were diagnosed with colon cancer during that time had had elevated CRP levels when they entered the study in 1989. CRP is a marker of inflammation already linked to increased risk of heart disease.
"If these findings are confirmed, it could provide new insights into the mechanisms underlying colorectal cancer, a new tool for risk identification/ stratification, and a new target for colorectal cancer prevention," said Dr. Ernest Hawk, chief of the Gastrointestinal and Other Cancer Research Group, NCI Division of Cancer Prevention.
NCI scientists have demonstrated that MS-275, a chemical proven to inhibit tumor cell growth in vivo, provides the added benefit of enhancing radiation-induced tumor cell killing. MS-275 inhibits histone deacetylase (HDAC), a protein that plays a critical role in modulating chromatin structure and regulating gene expression. HDAC is a protein target for chemotherapeutic agents because of its aberrant activity in tumor cells that causes the repression of tumor suppressor genes. In their study, published in the January 1 issue of Cancer Research, Dr. Kevin Camphausen and colleagues directly correlate the radiosensitizing effect to molecular events in the cell and suggest that this is due to inhibition of repair of DNA double-strand breaks.
The results were verified on two cancer cell lines, glioma and prostate carcinoma, which indicates that this may be a generally applicable strategy for enhancing tumor cell radiosensitivity in combined radio- and chemotherapy. MS-275 has recently entered into phase I clinical trials, and this work may aid in the design of in vivo combination therapy protocols. However, its applicability to other clinically relevant HDAC inhibitors will require further investigation.