Radiosensitization by a novel Bcl-2 and Bcl-XL inhibitor S44563 in small-cell lung cancer

• DOI: 10.1038/cddis.2014.365
• Publication Date: 2014-09-18T13:18:57Z
• Authors: Y Loriot; P Mordant; D Dugue; O Geneste; A Gombos; P Opolon; J Guegan; J-L Perfettini; A Pierre; L K Berthier; G Kroemer; J C Soria; S Depil; E Deutsch
• Keywords: Radiosensitivity; Clonogenic assay; Bcl-xL; Radioresistance

Radiotherapy has a critical role in the treatment of small-cell lung cancer (SCLC). The effectiveness radiation SCLC remains limited as resistance results from defects apoptosis. In current study, we investigated whether using Bcl-2/Bcl-XL inhibitor S44563 can enhance radiosensitivity cells vitro and vivo. studies confirmed that caused to acquire hallmarks markedly enhanced sensitivity radiation, determined by clonogenic assay. combination cisplatin-based chemo-radiation showed significant tumor growth delay increased overall survival mouse xenograft models. This positive interaction was greater when given after completion which might be explained radiation-induced overexpression anti-apoptotic proteins secondary activation NF-κB pathway. These data underline possibility combining IR inhibition they underscore importance administering conventional targeted therapies an optimal sequence.