Cancer

Patient sample, cell culture and mouse studies suggest inhibiting the TRIB3-PML interaction could help treat APL. In AML patients, bone marrow levels of TRIB3 were higher in than in healthy volunteers. In primary macrophages and granulocytes from a mouse model of APL, knockout of TRIB3 decreased colony formation compared with normal expression. In primary hematopoietic progenitor cells from the model, a peptide inhibitor of the TRIB3-PML interaction plus all-trans retinoic acid (ATRA) decreased colony formation compared with the peptide plus vehicle or a scrambled peptide plus ATRA. In a xenograft mouse model of APL, tumor-specific TRIB3 knockdown increased survival and decreased tumor growth compared with normal TRIB3 expression. In the two APL models, the peptide inhibitor plus ATRA or Trisenox arsenic trioxide increased survival compared with any agent alone. Next steps could include identifying and testing small molecule TRIB3-PML inhibitors in models of APL.

The generic ATRA is marketed for APL, acne and other skin conditions...