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Current systemic therapies for breast cancer are often limited by their nonspecific mechanism of action, unwanted toxicities on normal tissues, and short-term efficacy due to the emergence of drug resistance. However, identification of the molecular abnormalities in cancer, in particular the key proteins involved in abnormal cell growth, has resulted in development of various signal transduction inhibitor drugs as new treatment strategies against the disease. Protein farnesyltransferase inhibitors FTIs were originally designed to target the Ras signal transduction pathway, although it is now clear that several other intracellular proteins are dependent on post-translational farnesylation for their function.
Tipifarnib INN : proposed trade name Zarnestra is a farnesyltransferase inhibitor. Farnesyltransferase inhibitors block the activity of the farnesyltransferase enzyme by inhibiting prenylation of the CAAX tail motif, which ultimately prevents Ras from binding to the membrane, rendering it inactive. C, with registration number R
Clinical trials are research studies that involve people. The clinical trials on this list are studying Tipifarnib. All trials on the list are supported by NCI. Clinical trials look at new ways to prevent, detect, or treat disease.
Duncan Building, CPB5. Background Tipifarnib is an orally active, competitive inhibitor of farnesyltransferase which has shown encouraging signs of activity either alone or when combined with other agents. Clinical studies of tipifarnib in combination with anti-estrogen therapy have yielded disappointing results.
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The San Diego-based drugmaker this week announced that in a single-arm, Phase II trial, researchers screened patients with relapsed or refractory urothelial cancer, identifying 15 who harbor HRAS mutations. Among 13 evaluable patients, five saw their tumors shrink and four had progression-free survival for more than six months. Two of the 15 patients withdrew from the study before their first response to the drug could be evaluated.
A copy of the poster is available on the Company's website at www. However, many other tumors such as T- and B-cell lymphomas, myeloid leukemias, pancreatic or breast cancers, in which anecdotal evidence of tipifarnib activity has been reported, do not usually carry HRAS mutations. We believe the preliminary results reported at ASH validate our observation that the CXCL12 pathway is a therapeutic target of tipifarnib and provide a potential path to expand the development of tipifarnib well beyond HRAS mutant solid tumors by using CXCLrelated biomarkers to enrich for patients most likely to benefit from treatment.
Study record managers: refer to the Data Element Definitions if submitting registration or results information. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining tipifarnib with trastuzumab may kill more tumor cells.