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Immunotoxins: The Next Generation
New Cancer-Related Mutations Found in Breast & Colon Cancers
News from the AACR’s Molecular Diagnostics in Cancer Therapeutic Development Meeting
News from the AACR’s Frontiers in Cancer Prevention Research Meeting
Panitumumab approved for metastatic colorectal carcinoma
Bevacizumab use expanded to lung cancer
Histone deactylase inhibitor, vorinostat, now available
Trastuzumab expanded to adjuvant use in breast cancer
Imatinib: New uses approved, cardiac warning issued
Targeted mouse models useful in testing novel anticancer agents
Reviewed by Nicholas J. Vogelzang, MD
The gene mutation that characterizes a moderate response to imatinib in the treatment of gastrointestinal stromal tumors (GIST) confers benefit when sunitinib is used, and a different GST tumor mutation predicts the opposite—a better response to imatinib than to sunitinib, according to researchers from the Oregon Health and Science University, Portland, reported at the AACR’s Molecular Diagnostics in Cancer Therapeutic Development Meeting, held in Chicago, Illinois, in September 2006. Their work provides important information about how the mutational status of a patient’s tumor can predict response to different targeted therapies.
The various mutations present on the tyrosine kinase enzyme can predict the degree of benefit obtained from imatinib therapy.
According to Michael C. Heinrich, MD, professor of medicine, the various mutations present on the tyrosine kinase enzyme can predict the degree of benefit obtained from imatinib therapy. For example, 85% of patients with GIST have a mutation in their tumor cell’s c-kit gene, which encodes a tyrosine kinase receptor, and the two thirds of those patients who mutation occurs in exon 11 of the molecule have the longest average response to imatinib. However, these tumors often mutate again and become resistant to imatinib. The 10%-15% of patients with a mutation in exon 9 do not respond as well to the drug but are less likely to mutate again. Those with no mutations show the least benefit.
Among patients resistant to imatinib, those with tumors that are wild type or have an exon 9 mutation have longer survival when treated with sunitinib than do those with an exon 11 mutation, the researchers found. They also discovered that 62% of tumors with exon 11 mutations mutated again, and that some of these secondary mutations respond to sunitinib whereas others do not.
According to Dr. Heinrich, these results suggest that patients with exon 11 mutations should remain on imatinib for a longer period of time before switching to sunitinib, and that a switch to sunitinib might occur earlier in patients with cancers with exon 9 mutations or no mutations.
Imatinib is available from Novartis Oncology as Gleevec, and sunitinib is produced by Pfizer, Inc, under the trade name of Sutent.
Biomarkers of Response to VEGF–Targeted Therapy Found in Renal Cell Carcinoma
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Biomarkers of Response to VEGF–Targeted Therapy Found in Renal Cell Carcinoma