PRT062607

Further, we proved that PRT could prevent post-ovariectomy (OVX) loss of bone and breast cancer-induced bone destruction in vivo, which agreed with the in vitro outcomes. In conclusion, our findings suggest the potential value of PRT in managing osteolytic diseases mediated by osteoclasts.

We found drug response profiles to be correlated closely for drugs targeting the same signaling-pathway, e.g. the B-cell receptor inhibitors Ibrutinib (BTK) and PRT062607 (Syk) (Pearson correlation coefficient: r=0.78, 95% CI: 0.72 - 0.83)...3) The microenvironmental stimulus and the drug exhibited no major individual effect on CLL cell survival, but together significantly increased CLL cell viability (e.g. Interferon-γ:Ralimetinib, p-value: < 0.0001)...A high signaling activity of IL-4 was associated with shorter time to treatment, indicating that CLL progresses faster with strong microenvironmental support. Conclusion We present a systematic investigation on the tumor microenvironment in CLL, the underlying molecular determinants as well its interference with drug response which will serve as a scientific resource and starting point for further mechanistical investigations.