期刊
CANCER DISCOVERY
卷 1, 期 7, 页码 562-572出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-11-0249
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资金
- Intellikine
- University of California Industry
Several phosphoinositide 3-kinase (PI3K) inhibitors are in the clinic and many more are in preclinical development. CAL-101, a selective inhibitor of the PI3K delta isoform, has shown remarkable success in certain hematologic malignancies. Although PI3K delta signaling plays a central role in lymphocyte biology, the degree of single-agent therapeutic activity of CAL-101 during early-phase development has been somewhat unexpected. CAL-101 works in part by blocking signals from the microenvironment that normally sustain leukemia and lymphoma cells in a protective niche. As PI3Ks enter the arena of molecular-targeted therapies, CAL-101 provides proof of principle that isoform-selective compounds can be effective in selected cancer types and patient populations. SIGNIFICANCE: A key question is whether compounds targeting a single PI3K catalytic isoform can provide meaningful single agent efficacy in cancer cells that express multiple isoforms. Clinical studies of the drug CAL-101 have provided a significant advance by showing that selective targeting of PI3K delta achieves efficacy in chronic lymphocytic leukemia, in part through targeting the tumor microenvironment. Cancer Discovery; 1(7); 562-72. (C) 2011 AACR.
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