Gleevec and Sprycel for sarcoma – pro
Sprycel is currently in trials for various types of srcoma. I found several other trials in different types of sarcoma.
An ongoing multi-institutional study by the Sarcoma
Alliance for Research Through Collaboration (SARC)
consortium is evaluating the activity of imatinib in non-
GIST sarcoma subtypes based on the postulated mechanism
of action involving inhibition of polymorphisms of
PDGFR and/or downstream effectors. Early results
demonstrate a progression-free survival benefit in
liposarcoma, leiomyosarcoma, and fibrosarcoma; however,
the final results have not been published.8 The Children’s
Oncology Group has recently published results of
a phase II study of imatinib in refractory solid tumors
that demonstrated no benefit in pediatric sarcoma.
Dasatinib, a small-molecule inhibitor of Src kinase
activity, is a promising cancer therapeutic agent with oral
bioavailability. Currently, dasatinib is approved for use in
imatinib-refractory chronic myelogenous leukemia. The
therapeutic potential of dasatinib was evaluated in 12
soft tissue and bone sarcoma cell lines. Dasatinib inhibited
Src kinase activity at nanomolar concentrations (3 to
68 nM) all 11 of the cell lines that exhibited activated Src
kinase activity. Inhibition of Src signaling was accompanied
by blockade of cell migration and invasion, consistent
with Src inhibition. Moreover, apoptosis was induced
in the osteosarcoma and Ewing’s subset of bone
sarcomas at nanomolar concentrations of dasatinib, indicating
that these bone sarcoma cell lines are dependent
on Src activity for survival. These results demonstrate
that dasatinib inhibits migration and invasion of diverse
sarcoma cell types and selectively blocks the survival of
bone sarcoma cells. Therefore, dasatinib might provide
therapeutic benefit by preventing the growth and metastasis
of sarcomas in patients.
Sprycel is promising but there are no published trials of Sprycel that I could find.