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 About UsSignificant Medical Breakthroughs Resulting from ICRF-funded Research Research by Israeli scientists funded by ICRF has led to many important medical breakthroughs and to the development of cancer drugs used around the world that save lives. These include: Velcade: a Drug for Treating Cancer of the Bone Marrow;
Five years after Dr. Hershko started his research, his team at Technion, including his student at the time, Dr. Aaron Ciechanover, discovered the system that degrades proteins - the ubiquitin system. "We found that a small protein, called ubiquitin, marks the proteins to be degraded at the right time and the right place in the cell," Dr. Hershko relates." If proteins are not degraded at the right time, the cell continues to divide unchecked. This is what happens in many cancer cells; something has gone wrong in the ubiquitin system." ICRF's Scientific Review Panel recognized the potential of this research. Dr. Ciechanover was a post-doctoral fellow at MIT and wanted to return to Israel to continue his research and studies, but he needed funding. He was awarded an ICRF Research Career Development Award in 1985, which enabled him to realize his talent and potential in Israel. ICRF has been funding him and this research into the process of protein degradation ever since. In 2003, Drs. Hershko and Ciechanover ICRF were each awarded ICRF Professorships, the highest designation, in 2002 and 2003 respectively. Each is receiving a grant of $50,000 a year for seven years. Dr. Hershko is The ICRF Nathan Galston Research Professor (from ICRF's Los Angeles chapter) and Dr. Ciechanover is The ICRF Harvey & Gloria Kaylie Research Professor (New York chapter). The Food and Drug Administration announced the approval of Velcade in May 2003, terming it, "the first in a new class of anticancer agents known as proteasome inhibitors." Millennium Pharmaceuticals of Cambridge, Mass., which developed Velcade, stated that it represents a "completely new approach to treating cancer." Multiple myeloma is the second most prevalent blood cancer after non-Hodgkin's lymphoma, according to the FDA. It is a cancer of the plasma cell, an important part of the immune system that produces antibodies to help fight infection and disease. Velcade is the "first drug specifically targeted against the ubiquitin system. It was developed based on this basic research done in my lab," Dr. Hershko said. "I am sure that many other new drugs will be discovered which are targeted against specific processes that go wrong in the ubiquitin system in different types of cancer. These include cancer of the colon, breast, prostate and melanomas." In 2000, Professors Hershko and Ciechanover received the prestigious Albert and Mary Lasker Award for Basic Medical Research, along with Dr. Alexander Varshavsky of the California Institute of Technology, "for the discovery and the recognition of the broad significance of the ubiquitin system of regulated protein degradation, a fundamental process that influences vital cellular events." This award is often a precursor to the Nobel Prize. They have each also received The Israel Prize, Israel's highest civilian honor, awarded for excellence in the sciences, humanities and the arts, and for special contributions to society and the State of Israel. And on December 10, 2004, Professors Hershko and Ciechanover, along with Dr. Irwin Rose of the University of California, were awarded the 2004 Nobel Prize in Chemistry for this research. "I am very grateful to the Israel Cancer Research Fund for supporting the work of cancer researchers in Israel, including my own research, which produces novel approaches to cancer treatment, such as Velcade" said Dr. Hershko. "ICRF seeded my scientific trip," Dr. Ciechanover noted. "My research is a product of ICRF." Gleevec: a Drug for Treating Leukemia
Gleevec is the result of decades of research on the molecular biology of cancer by many brilliant scientists set on the identification and characterization of mutations which cause cancer -- an area where Dr. Canaani has been a pioneer. Dr. Canaani, together with Dr. Robert Gale and Dr. Emma Shtivelman at Weizmann, and other researchers including Dr. John Groffen of the National Cancer Institute, Dr. Owen Witte of UCLA Medical School, and Dr. David Baltimore, president of CalTech, discovered the molecular consequences of the formation of the so-called "Philadelphia chromosome," a well-known marker for CML. Working independently, these researchers demonstrated that the Philadelphia chromosome, which results from swapping portions of chromosome 9 and 11, encodes a novel protein composed of elements of the abl and bcr proteins derived from chromosomes 9 and 11, respectively. This new protein, in essence an uncontrolled form of abl, slips into the cellular signaling machinery to directly initiate CML. Gleevec effectively binds to and blocks the action of this CML-specific protein. While Gleevec, manufactured by Novartis, was used initially to treat CML and a rare form of stomach tumor, researchers see great potential for its use against other major cancers. It is one of the very first examples of a whole new class of anti-cancer drugs targeted against specific proteins. In contrast to other drug types which harm any individual cell, healthy or not, Gleevec appears to kill only the cells producing the dangerous CML-specific protein.  Doxil: a Drug Used in the Treatment of Breast and Ovarian Cancer He was a major contributor to the discovery and development of Doxil -- a compound based on lipid (fatty) submicroscopic particles known as liposomes loaded with the anticancer agent doxorubicin, and used in the treatment of breast cancer, ovarian cancer and Kaposi's sarcoma, a form of cancer in AIDS patients. The FDA approved the drug in 1996 and it was on pharmacies' shelves a year later. "Doxil," Dr. Gabizon explained, "directs drugs to the diseased tissues only, not to the rest of the patient's body, and releases them slowly. This greatly reduces the side effects normally associated with chemotherapy. The impact of Doxil on the efficacy and safety of treatment of advanced ovarian and breast cancer is already evident in the clinical practice. I am confident that further clinical research will establish the potential of Doxil in the treatment of a variety of other metastatic tumors, which remains so far largely untapped." "The commitment of ICRF played a significant role in allowing us to proceed with this long-term project and bring it to completion in our research laboratory," Dr. Gabizon noted. "ICRF has made a real difference in elevating the quality of Israeli science and in maintaining its standing in the international scientific community," he declared. "Supporting more than 50 research laboratories in Israel is very significant in our small country, where funding available for medical research is very limited." "Donating to research requires vision and courage." RAD51: a Key Genetic Factor For Higher Breast and Ovarian Cancer Risk  Dr. Ephrat Levy-Lahad , an ICRF-funded scientist at Shaare Zedek Medical Center in Jerusalem, and her team examined 57 carriers of BRCA1 and BRCA2 mutations to learn why. They discovered another genetic abnormality that significantly increases the likelihood for developing cancer among women with the BRCA2 gene mutation. Dr. Levy-Lahad found that a minor mutation in a different gene, RAD51, greatly elevated the risk for BRCA2 mutation carriers. Previously, there had been no indicators among women with either of the BRCA mutations as to who would contract the disease, at what age, and with what severity. Dr. Levy-Lahad believes there may be other factors that could trigger the disease, but the role of RAD51 has now been established as central. This discovery is particularly important to the one-out-of-forty Jewish women of Eastern European ancestry who have the BRCA1 or BRCA2 mutations. These mutations, which are found at much lower rates in Sephardi and non-Jewish women, account for some 10 percent of breast cancer and 30 percent of ovarian cancers. Until this discovery, breast cancer specialists had been uncertain as to what course of action to suggest to women who carry the mutated BRCA1 and 2 genes. These findings allow doctors to distinguish those women who are at high risk for developing breast cancer from women who are at a low risk by providing very important guidance for oncologists. At the same time, this discovery will save many women from unnecessary anxiety (BRCA2 mutation carriers who do not have the mutated RAD51 gene), while benefiting other women through early preventative intervention. "A test for RAD51 could become a routine part of testing for BRCA2 mutation carriers," Dr. Levy-Lahad said. "If further studies confirm these results, aggressive preventive treatment, including surgery, might then be recommended for women with both genes." P53: a Key Tumor Suppressor ICRF also funded further research by his colleague at Weizmann, Dr.Varda Rotter, who explored the genetic machinery of cancer cells and the role that p53 plays in malignancy. Many cancer researchers now consider the p53 gene to be a possible key to the cure for cancer.  DNA Methylation; Deciphering the Genetic Defects That Lead To Cancer He noted that tumors result from an imbalance in the gene regulation machinery of the cell. The objective of his study of the regulation of gene expression in animal cells is to understand the process whereby genes in living organisms are turned on and off during development. He led a team of researchers at Hebrew University/Hadassah Medical School that took an important step in comprehending this process, which has significant consequences for advancing the use of medical genetic engineering -- growing new tissue to replace damaged or defective organs, or halting the growth of undesirable tumors. The achievement took nearly five years of research to attain. These new findings provide information fundamental to understanding how an embryo develops and for deciphering the genetic defects that lead to cancer. This data will also aid scientists in developing better methods for therapeutic genetic engineering. Dr. Cedar, Professor in the Department of Cellular Biochemistry at Hebrew University/Hadassah Medical School, explained that in general there are two kinds of genes in every cell -- those that control the "housekeeping" duties necessary to keep all cells functioning, and those that give each tissue its unique properties. Since a complete set of genes exists in every cell, no matter where it is located in a given organism, most tissue-specific genes are actually in a dormant, unexpressed state. Only those genes needed for a particular cell type (such as liver, heart, or brain) are activated, along with the housekeeping genes. How are some genes kept on while others are turned off? Dr. Cedar's new studies suggest that this occurs during the process of gene duplication which occurs before cell division. Housekeeping genes get copied early during a unique "window of opportunity" that activates them, while other genes are copied later. The latter, as a result, are mostly doomed to inactivity. He drew an analogy. "If you try to do something when a timer clock is off, you won't be able to do anything; you can do it only when the timer is on." Thus, in a sense, each cell knows how to pass on to the next generation both the genes themselves and the instructions for setting up their state of activity or inactivity -- their timer mechanism.  Bone Marrow Transplant For Leukemia Patients |
Velcade is the result of thirty years of research by Israeli scientists, initiated by Professor Avram Hershko of Technion-Israel Institute of Technology in Haifa, into how proteins are degraded in cells. Proteins, Dr. Hershko explains, are the "machines that carry out and regulate all the processes in the cells. But once a protein has done its job, it has to be disposed of. We needed to understand this process of protein degradation."
For many years, ICRF has supported the work of one of the leading scientists who played a key role in the complex research that led to Gleevec, the revolutionary new anti-cancer drug for the treatment of chronic myelogenous leukemia (CML): Dr. Eli Canaani of The Weizmann Institute of Science.