CUDC-907 Modulates Expression of Certain Cytokines/ Chemokines, Potentially Targeting Tumor Microenvironment in Addition to Direct Effects on Cancer Cells
Sensitivity to CUDC-427 May Be Predicted by Alterations in TNF-α and XIAP Expression
LEXINGTON, Mass., April 7, 2014 (GLOBE NEWSWIRE) -- Curis, Inc. (Nasdaq:CRIS), an oncology-focused company developing novel, targeted drug candidates for the treatment of human cancers, today announced that it reported data from in vitro studies and a translational biomarker analysis for CUDC-907, a dual histone deacytelase (HDAC) and phosphoinositide 3-kinase (PI3K) inhibitor, as well as results from in vitro and in vivo studies for CUDC-427, an antagonist of inhibitor of apoptosis (IAP) proteins, at the American Association for Cancer Research (AACR) 2014 Annual Meeting. CUDC-907 is being investigated in a Phase 1 trial in patients with relapsed/refractory lymphoma or multiple myeloma. CUDC-427 is being studied in a Phase 1 trial in patients with advanced solid tumors or lymphoma.CUDC-907 Presentation Curis scientists presented an abstract entitled " Dual function HDAC and PI3K inhibitor, CUDC-907 affects cancer cells and the tumor microenvironment in hematological malignancies" on Monday, April 7, 2014.The poster presentation included data from cell-based hematologic models suggesting that, in addition to direct effects on cancer cells, CUDC-907 may also alter the tumor microenvironment as measured by changes in the levels of certain cytokines and chemokines. Exposure of Hodgkin's lymphoma, diffuse large B-cell lymphoma and multiple myeloma cell lines to CUDC-907 resulted in reduction in the levels of CCL17 (TARC), a chemokine involved in the stimulation and proliferation of helper T cells required for the survival of certain malignant blood cells. Preliminary data from patients with lymphoma treated with CUDC-907 in the ongoing Phase 1 study suggested correlative trends between patient benefit and plasma TARC levels prior to treatment, as well as potential correlations between tumor response and plasma TARC level changes induced by 15 days of CUDC-907 treatment. Further analysis of plasma cytokine and chemokine levels is ongoing to explore TARC and other molecules as markers/predictors of CUDC-907's activity, which may also inform patient stratification strategies.