RT Journal Article SR Electronic T1 Inhibition of Retinoblastoma Cell Growth by CEP1347 Through Activation of the P53 Pathway JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 4961 OP 4968 DO 10.21873/anticanres.14499 VO 40 IS 9 A1 KEITA TOGASHI A1 MASASHI OKADA A1 SHUHEI SUZUKI A1 TOMOMI SANOMACHI A1 SHIZUKA SEINO A1 MASAHIRO YAMAMOTO A1 HIDETOSHI YAMASHITA A1 CHIFUMI KITANAKA YR 2020 UL http://ar.iiarjournals.org/content/40/9/4961.abstract AB Background/Aim: Despite advances in treatment modalities, the visual prognosis of retinoblastoma still remains unsatisfactory, underscoring the need to develop novel therapeutic approaches. Materials and Methods: The effect on the growth of six human retinoblastoma cell lines and a normal human fibroblast cell line of CEP1347, a small-molecule kinase inhibitor originally developed for the treatment of Parkinson's disease and therefore with a known safety profile in humans, was examined. The role of the P53 pathway in CEP1347-induced growth inhibition was also investigated. Results: CEP1347 selectively inhibited the growth of retinoblastoma cell lines expressing murine double minute 4 (MDM4), a P53 inhibitor. Furthermore, CEP1347 reduced the expression of MDM4 and activated the P53 pathway in MDM4-expressing retinoblastoma cells, which was required for the inhibition of their growth by CEP1347. Conclusion: We propose CEP1347 as a promising candidate for the treatment of retinoblastomas, where functional inactivation of P53 as a result of MDM4 activation is reportedly common.