| First Author | Fruman DA | Year | 2011 |
| Journal | Cancer Discov | Volume | 1 |
| Issue | 7 | Pages | 562-72 |
| PubMed ID | 22586681 | Mgi Jnum | J:193070 |
| Mgi Id | MGI:5467485 | Doi | 10.1158/2159-8290.CD-11-0249 |
| Citation | Fruman DA, et al. (2011) PI3Kdelta inhibitors in cancer: rationale and serendipity merge in the clinic. Cancer Discov 1(7):562-72 |
| abstractText | Several phosphoinositide 3-kinase (PI3K) inhibitors are in the clinic and many more are in preclinical development. CAL-101, a selective inhibitor of the PI3Kdelta isoform, has shown remarkable success in certain hematologic malignancies. Although PI3Kdelta 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 PI3Kdelta achieves efficacy in chronic lymphocytic leukemia, in part through targeting the tumor microenvironment. |
