Thursday, May 1, 2014
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sclerosis complex tumor suppressor 2 (TSC2)
Studies in patient samples,
cell culture and mice suggest inhibiting Src kinase activity could help treat
the progressive cystic lung disease lymphangioleiomyomatosis (LAM). LAM
commonly affects patients who have mutations in TSC2. In samples from
patients with LAM and in a Tsc2-deficient rat fibroblast cell line,
Src phosphorylation levels were greater than those in normal samples and
wild-type fibroblasts. In mice, the Src kinase inhibitor saracatinib
decreased lung colonization by Tsc2-deficient rat fibroblasts injected
into the peritoneum compared with vehicle. Next steps include clinical trials
to evaluate Src kinase inhibitors to treat LAM.
plc's saracatinib, a dual inhibitor of Src and BCR-ABL
tyrosine kinases, has completed a
Phase IIb trial in ovarian cancer.
Squibb Co. and Otsuka
Pharmaceutical Co. Ltd. market Sprycel
a small molecule inhibitor of BCR-ABL and Src kinases, to treat acute
lymphoblastic leukemia (ALL) and chronic myelogenous leukemia (CML).
Inc. markets Bosulif
a dual inhibitor of BCR-ABL and Src kinases, to treat CML.
At least six other companies have Src kinase-inhibiting drug candidates in
Phase II testing or earlier to treat various cancers.
SciBX 7(17); doi:10.1038/scibx.2014.501
Published online May 1, 2014
Patent and licensing status
Tyryshkin, A. et al.
Cancer Res.; published online April 1, 2014;
Contact: N. Tony Eissa, Baylor College of Medicine, Houston,
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