Research by Type:
| Breast Cancer Research |
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BACKGROUND 1. Novel MRI contrast agent for a promising new biomarker NFCR scientist, James Basilion, Ph.D., is leading his team at Case Western Reserve University in Cleveland, Ohio, in the development of the "next generation" of highly sensitive imaging technologies that will allow earlier detection of tumors and consequently produce higher cure rates. The scientists continue to develop imaging probes against CRIP-1, a breast cancer marker expressed in abnormally high amounts in 90% of breast cancer cases. CRIP-1 is an ideal genetic marker for detecting breast cancer at its earliest stage, when it cannot be detected using current technologies. Recently, the team began investigating the use of a novel MRI contrast agent which will increase the sensitivity of imaging by 10 to 100 times over present technology. This will allow doctors to directly see the changes in the production and location of the CRIP-1 molecules in breast cancer cells, and greatly assist them in conducting a more appropriate and personalized diagnostic analysis for each patient in the earliest stage of their illness. 2. Nanotechnology drug delivery tools to target metastasis and enhance chemotherapy Only about 30% of breast cancer patients are deemed eligible for the anti-HER-2 antibody treatment because their breast cancer cells express high levels of the tumor promoting molecule HER-2. However, even low levels of the HER-2 protein may promote abnormal growth, and a strategy that targets tumors with varying levels of HER-2 would likely help more breast cancer patients. Dr. Esther Chang, NFCR scientist at Georgetown University in Washington, D.C., has developed one such strategy with her "nanoparticle". In fact, this powerful technology is presently in phase I clinical trials for treatment of patients with several types of solid tumors. The tiny but smart nanoparticle-about one-thousandth smaller than a printed period-homes in only on cancer cells, delivering anti-HER-2 agents to the inside of both primary and metastatic tumors. Dr. Chang's pre-clinical results show the size of tumors with low HER-2 levels is greatly reduced when these "smart" agents are combined with chemotherapy. The data also demonstrate that anti-HER-2 nanotechnology makes breast cancer cells more sensitive to chemotherapy, suggesting that patients may be given lower doses of chemotherapy and experience less debilitating side effects. With continued success in Dr. Chang's pre-clinical research, this innovative cancer therapy combined with chemotherapy may advance to clinical trials to treat breast cancer patients with high and low levels of HER-2, providing many more women with an effective anti-HER2 treatment for their cancer. 3. Determining which patients will respond to Taxol, one of the most widely used Taxol, a natural product from the yew tree, has been used to treat over a million cancer patients with lung, breast and ovarian cancer. The broad use of Taxol has, in part, been credited to internationally known NFCR scientist, Susan Band Horwitz, Ph.D., at the Albert Einstein College of Medicine in Bronx, New York. Dr. Horwitz discovered the molecular mechanism of Taxol-that it binds and inhibits tubulin, a protein crucial to cell growth. Not every patient treated with Taxol responds well to the drug, however, and this, according to Dr. Horwitz, may be due to the ability of cancer cells to alter the type of tubulin proteins they express, rendering Taxol "off the target". To focus on this very important issue, she recently developed new techniques that enable her team to isolate and identify the different types of tubulin expressed in breast cancer cells as compared to normal cells. Importantly, the scientists will be able to learn if different types of tubulin proteins have varying sensitivity to Taxol. Dr. Horwitz's research is of high impact as it may be possible, by analyzing the type of tubulin expressed in a patient's cancer cells, to determine if they will respond effectively to Taxol even before the onset of treatment. 4. Targeting rare breast cancer cells that may cause cancer to return after treatment Kathryn Horwitz, Ph.D., NFCR scientist at the University of Colorado Health Science Center in Aurora, Colorado, is world renowned for her work on the development and treatment of hormone-dependent breast cancers-those that are positive for estrogen and progesterone receptors (ER+PR+). 30% or more of ER+PR+ cancer patients see their tumor return after being "cancer-free" for years, even decades, following anti-hormone and chemotherapy treatments. Dr. Horwitz believes that these tumors contain a rare type of "treatment-resistant" cell-that remains dormant or asleep, only to reawaken years later and grow new tumors. With a new method developed by Dr. Horwitz, her team of scientists already has identified treatment-resistant cells in tumor samples from patients after a short-term anti-hormone therapy. The group is now actively looking for these cells in tumor biopsy samples from patients whose cancer has returned after ten years - this is to confirm that treatment-resistant cells do survive long dormant periods and then begin growth of new tumors. Meanwhile, the team is also developing breast cancer treatment-resistant cell lines to identify biomarkers for the development of therapeutic agents that can kill these cells. With the work by Dr. Horwitz and her dedicated team, it is now possible that in the foreseeable future, ER+PR+ breast cancer patients may no longer need to fear for their cancer to return. 5. Metastasis suppressor genes and proteins: stopping the real killer of breast cancer patients Danny Welch, Ph.D., Director of the NFCR Center of Metastasis Research, University of Alabama (Birmingham) and his collaborators have discovered six metastasis suppressor genes -opening the research doors towards identifying key players in the complex biology of metastatic cancer. Two of the genes, KISS1 and BRMS1, are found in metastatic breast cancer and the scientists are determining how the protein products of these genes function to keep cancer cells from spreading. They have demonstrated that KISS1 proteins are processed in the cell to become smaller proteins called kisspeptins, which have metastasis suppression abilities. Dr. Welch's team is now identifying cellular proteins that interact with kisspeptins-an important next step to reveal how kisspeptins mediate suppression of metastasis. Once the scientists know the partners of kisspeptins, they can design molecules that mimic them, leading to the development of novel anti-cancer therapies that prevent metastasis from happening or keep it dormant. If this can be achieved, it could bring the cancer under control and give patients a more promising opportunity for a cure and a longer life. . 6. Defining targets to stop breast cancer cells' ability to leave their primary tumor sites. Researchers believe the genes that make healthy cells migrate and become new tissues during normal embryonic development may also contribute to abnormal processes used by cancer cells to invade nearby healthy tissue. This first step of invasion enables cancer cells to migrate through tissues, reach a blood vessel, circulate through the bloodstream (as rare circulating tumor cells or CTCs), and may eventually grow into a deadly tumor at a distant site in the body through metastasis. NFCR scientist, Daniel Haber, M.D., Ph.D. of Massachusetts General Hospital, is using a highly innovative two-step approach to identify genes involved in cancer cell invasion. First, Dr. Haber's team screened gene libraries and identified 45 candidate genes for normal and abnormal cell migration and invasion. With additional screening, a key subset of genes will be further refined from the list. Next, the identified genes will be examined to confirm their activity and function during tumor invasion. CTCs are rare in the bloodstream and it has been challenging to conduct research on these cells. But this is now possible thanks to a breakthrough technology developed by Dr. Haber. The CTC Chip, similar in size to a business card, uses nanotechnology to isolate the very rare CTCs from cancer patients' blood. The CTCs collected on the Chip from blood samples of metastatic breast cancer patients will be analyzed for activities of the candidate genes for cancer migration and invasion. This innovative research plan may identify novel molecules that can serve as either biomarkers of cancer cell invasion or as targets for development of therapeutic agents that will stop the early steps in cancer metastasis and prevent breast cancer cells from ever leaving the cancerous breast tissue. 7. Fighting breast cancer on a global scale NFCR is fighting breast cancer on a global scale with the establishment of the Tissue Bank Consortium in Asia (TBCA). Managed by NFCR, the TBCA is a group of biorepositories or state-of-the-art tumor tissue sample preparation and storage facilities in China. Fresh frozen and preserved tumor tissues are collected and both types of tissue are suitable for research with all the cutting-edge molecular techniques. The TBCA is connected to a data base that is accessible online for collaborating researchers from around the world. Once online, they can determine the availability of suitable cancer tissue samples, examine available data, and request information and research support. The TBCA currently contains more than 21,200 high quality cancer tissue samples, including more than 6,100 breast cancer samples-one of the world's largest single collections of breast cancer tissue. With this international research facility, collaborative efforts on genomic studies and tissue microarrays have already improved the classification of breast cancers and produced early diagnostic tests and more effective cancer therapies.
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