XPO1 inhibition synergizes with PARP1 inhibition in small cell lung cancer by targeting nuclear transport of FOXO3a

• Published in: Cancer letters Vol. 503; pp. 197 - 212
• Main Authors: Wang, Jingya, Sun, Tao, Meng, Zhaoting, Wang, Liuchun, Li, Mengjie, Chen, Jinliang, Qin, Tingting, Yu, Jiangyong, Zhang, Miao, Bie, Zhixin, Dong, Zhiqiang, Jiang, Xiangli, Lin, Li, Zhang, Cuicui, Liu, Zhujun, Jiang, Richeng, Yang, Guang, Li, Lin, Zhang, Yan, Huang, Dingzhi
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 10.04.2021; Elsevier Limited
• Subjects: Active Transport, Cell Nucleus - drug effects; Animals; Antibodies; Antigens; Apoptosis; Cancer therapies; Cell Line, Tumor; Cell Nucleus - metabolism; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Clinical trials; CRISPR; Cytoplasm; Cytoplasm - metabolism; Deoxyribonucleic acid; DNA; DNA damage; Drug Synergism; Exportin 1 Protein; Female; Forkhead Box Protein O3 - metabolism; Forkhead protein; FOXO3 protein; FOXO3a; Gene Expression Regulation, Neoplastic - drug effects; Humans; Hydrazines - administration & dosage; Hydrazines - pharmacology; Immunoprecipitation; Karyopherins - antagonists & inhibitors; Kinases; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Mass spectrometry; Medical prognosis; Mice; Nuclear translocation; Nuclear transport; PARP inhibitor; Phosphorylation; Phthalazines - administration & dosage; Phthalazines - pharmacology; Poly(ADP-ribose) polymerase; Proteins; Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors; Ribose; Scientific imaging; Small cell lung cancer; Small cell lung carcinoma; Small Cell Lung Carcinoma - drug therapy; Small Cell Lung Carcinoma - metabolism; Toxicity; Transcription factors; Triazoles - administration & dosage; Triazoles - pharmacology; Xenograft Model Antitumor Assays; Xenografts; XPO1 inhibitor; IHC; CCLE; IKKs; HR; PARP; ChIP; mini-PDX; DDR; XPO1; qPCR; ITRAQ; PFS; SCLC; KOG; SSB; OS; CI; PARP inhibitor; GO; Akt; Co-IP; Small cell lung cancer; MMR; Nuclear translocation; XPO1 inhibitor; FOXO3a; HE

Patient mortality rates have remained stubbornly high for the past decades in small cell lung cancer (SCLC) because of having no standard targeted therapies with confirmed advantages at present. Poly [ADP-ribose] polymerase (PARP) inhibitors have shown promise in preclinical models but have had unsa...