Januario E. Castro, M.D. University of California, San Diego

THERAPY/ PROGNOSTIC

Targeting ZAP-70 Tyrosine Kinase in Chronic Lymphocytic Leukemia

Update:

We have identified and validated a new independent prognostic marker for patients with CLL based on an assay that measures activation of the protein Hsp90. This test can potentially identify, at the time of diagnosis, patients that may have a more aggressive clinical course in spite of having good prognostic markers such as low expression of ZAP-70.

We have completed testing on 60 additional samples out of 300 patients that constitute a validation cohort of this test. With this information, we are proposing to design a clinical test that can be used as a biomarker for disease activity and prognosis in CLL and other forms of cancer.

We have found a panel of genes that are differentially regulated in CLL cells that are undergoing cell death induced by Hsp90 inhibitors. These genes can be used to better understand the biological pathways used by Hsp90 inhibitors and also to evaluate the activity of Hsp90 inhibitors as treatment of patients with cancer. We believe that this set of genes will provide a valuable tool for the development of Hsp90 inhibitors in cancer.

More importantly, we have initiated a trial in which patients receive treatment with an Hsp90 inhibitor (CNF2024). This clinical trial is an early phase I dose escalation study in which six patients have received treatment. So far no serious adverse events have been observed, and dose escalation continues.