Environment-Mediated Drug Resistance in Neuroblastoma
Technical Report,30 Sep 2013,29 Sep 2014
CITY OF HOPE BECKMAN RESEARCH INST DUARTE CA DUARTE
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During the second year of funding, collaborative experiments have demonstrated that monocytes collaborate with MSC in inducing STAT3-dependent drug resistance in neuroblastoma Task 1, that S1PS1PR1 contributes to a sustainable STAT3 activation leading toward increased survival Task 2, and that Jak2 deletioninhibition prevents drug resistance Task 3. Experiments aimed at examining the effect of small pathway inhibitors suggest that inhibition of Jak2, MEK and S1PR1 all contribute to prevent drug resistance, but that inhibition of multiple pathways may be required Task 4. Experiments aimed at examining the role of IL-6 clearly demonstrate that although IL-6 is involved in STAT3-mediated drug resistance, it is not necessary as STAT3 is activated in IL-6 KO mice and tumors develop in IL-6 KO mice crossed with NB-Tag mice Task 5. As a result, Task 6 which focused on targeting IL-6 has been abandoned. Task 7 has now been initiated using a combination of S1PR1 and Jak2 inhibitors in vitro and in vivo.
- Medicine and Medical Research