1 reply to this topic

[TeddyB]

http://online.wsj.co...925-904896.html

" SL-401 significantly reduced the growth of CML blasts, as well as CSCs, from patients with tyrosine kinase inhibitor (TKI)-resistant CML. In addition, the combination of SL-401 and the TKI, imatinib (Gleevec), had a significant synergistic effect on inhibiting the growth of primary CML cells from patients. SL-401 also prolonged the survival of mice inoculated with primary cells from a CML patient in blast crisis who was resistant to several TKIs."

Comments?

[Trey]

SL-401 targets a "back door" survival mechanism which leukemia cells can use when TKIs shut down the BCR-ABL "front door".  It is an interleukin-3 receptor (IL-3R) inhibitor which may be able to close off a key survival mechanism for leukemia cells since they over-express IL-3R (all WBCs express IL-R3 to some degree, but leukemic ones to a greater degree).  So it has some promise, but no one knows how many potential "back door" survival mechanisms may exist.  And the higher the leukemic stem cell in the cell hierarchy, the more potential back door survival mechanisms exist.  But the strategy of shutting down the back door survival mechanisms will potentially help those who fail TKI drugs.  So it is a good strategy, but more such targeted drugs may be necessary.