High αvβ3 integrin and low PTEN expression neuroblastomas as target for dual PI3K/BRD4 inhibitor

Drs A. Erdreich-Epstein, D.L. Durden and colleagues have described how high αvβ3 integrin in microvessels and low PTEN in tumor cells, detected by IHC in neuroblastoma stage 3 tumors, predicts poor outcome in these patients. Stage 3 neuroblastoma tumors are difficult to classify and treat, as this group comprises both patients with tumors responsive to therapy and patients with aggressive resistant tumors. The phosphatase PTEN is found to regulate neuroblastoma tumor growth in animal models.

This study also provides a rationale for the use of the first-in-class dual PI3K/BRD4 inhibitor SF1126 to treat the group of stage 3 neuroblastoma patents with poor outcome, by targeting both high PI3K activity and metastatic-prone integrin expression on the tumor microenvironment.

Erdreich-Epstein A, Singh AR, Joshi S, Vega FM, Guo P, Xu J, Groshen J, e W, Millard M, Campan M, Morales G, Garlich JR, Laird PW, Seeger RC, Shimada H, Durden DL. Association of high microvessel αvβ3 and low PTEN with poor outcome in stage 3 neuroblastoma: rationale for using first in class dual PI3K/BRD4 inhibitor, SF1126. Oncotarget. 2016 Nov 16. doi: 10.18632/oncotarget.13386.

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