Chun Liu1, Chenxi Hu1, Ting Chen1, Yanting Jiang1, Xin Zhang2, Hongyu Liu3, Yuan Wang3, Zhi Li3, Kaiyuan Hui4, Xiaodong Jiang5. 1. Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222000, Jiangsu, People's Republic of China. 2. Lianyungang Clinical College of Nanjing Medical University, Lianyungang, 222000, Jiangsu, People's Republic of China. 3. Echo Biotech Co., Ltd, Beijing, People's Republic of China. 4. Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222000, Jiangsu, People's Republic of China. kyhui1987@163.com. 5. Department of Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, 222000, Jiangsu, People's Republic of China. jxdpaper@163.com.
Abstract
PURPOSE: Anlotinib is an oral small-molecule multitarget tyrosine kinase inhibitor that hampers neovascularization thus providing antitumor effect. The ALTER 0303 trial was a multicenter, double-blind, phase 3 randomized clinical study to evaluate the efficacy of anlotinib in patients with advanced non-small cell lung cancer (NSCLC). The ALTER 0303 results showed that patients in the anlotinib group had a median progression-free survival of 5.4 months, a significant improvement compared with 1.4 months in the placebo group; however, median overall survival was only extended by 3.3 months (9.6 vs 6.3 months). The problem of anlotinib resistance cannot be ignored, and an in-depth exploration of biomarkers of anlotinib treatment response is urgently needed to further improve the efficacy of anlotinib in the treatment of NSCLC. This study aimed to identify plasma exosome markers that could be used to monitor the efficacy of anlotinib. METHODS: We enrolled 5 patients with advanced NSCLC, and 15 blood samples were collected before anlotinib treatment, when the treatment was effective, and when the treatment was ineffective. The plasma exosomal RNA profiles were analyzed by whole-transcriptome sequencing at three different stages. The expression of dysregulated exosomal RNAs in 43 additional patients was also verified by real-time quantitative PCR. RESULTS: In the plasma exosomal RNA profiles of the 5 patients with advanced NSCLC during treatment with anlotinib, 7 miRNAs, 3 lncRNAs, and 83 mRNAs were significantly dysregulated. The regulation trend was opposite when the treatment was effective and ineffective, showing dynamic changes. After validation, we finally found that plasma exosomal lnc-SNAPC5-3:4 was significantly upregulated when anlotinib treatment was effective, and it was significantly downregulated when the treatment failed (p < 0.05). Thus, it can be used as a potential biomarker for monitoring the efficacy of anlotinib. CONCLUSION: Our results demonstrate the potential of plasma exosomal lnc-SNAPC5-3:4 as a biomarker for monitoring anlotinib efficacy.
PURPOSE: Anlotinib is an oral small-molecule multitarget tyrosine kinase inhibitor that hampers neovascularization thus providing antitumor effect. The ALTER 0303 trial was a multicenter, double-blind, phase 3 randomized clinical study to evaluate the efficacy of anlotinib in patients with advanced non-small cell lung cancer (NSCLC). The ALTER 0303 results showed that patients in the anlotinib group had a median progression-free survival of 5.4 months, a significant improvement compared with 1.4 months in the placebo group; however, median overall survival was only extended by 3.3 months (9.6 vs 6.3 months). The problem of anlotinib resistance cannot be ignored, and an in-depth exploration of biomarkers of anlotinib treatment response is urgently needed to further improve the efficacy of anlotinib in the treatment of NSCLC. This study aimed to identify plasma exosome markers that could be used to monitor the efficacy of anlotinib. METHODS: We enrolled 5 patients with advanced NSCLC, and 15 blood samples were collected before anlotinib treatment, when the treatment was effective, and when the treatment was ineffective. The plasma exosomal RNA profiles were analyzed by whole-transcriptome sequencing at three different stages. The expression of dysregulated exosomal RNAs in 43 additional patients was also verified by real-time quantitative PCR. RESULTS: In the plasma exosomal RNA profiles of the 5 patients with advanced NSCLC during treatment with anlotinib, 7 miRNAs, 3 lncRNAs, and 83 mRNAs were significantly dysregulated. The regulation trend was opposite when the treatment was effective and ineffective, showing dynamic changes. After validation, we finally found that plasma exosomal lnc-SNAPC5-3:4 was significantly upregulated when anlotinib treatment was effective, and it was significantly downregulated when the treatment failed (p < 0.05). Thus, it can be used as a potential biomarker for monitoring the efficacy of anlotinib. CONCLUSION: Our results demonstrate the potential of plasma exosomal lnc-SNAPC5-3:4 as a biomarker for monitoring anlotinib efficacy.
Authors: Domènec Farré; Romà Roset; Mario Huerta; José E Adsuara; Llorenç Roselló; M Mar Albà; Xavier Messeguer Journal: Nucleic Acids Res Date: 2003-07-01 Impact factor: 16.971
Authors: Oriol Fornes; Jaime A Castro-Mondragon; Aziz Khan; Robin van der Lee; Xi Zhang; Phillip A Richmond; Bhavi P Modi; Solenne Correard; Marius Gheorghe; Damir Baranašić; Walter Santana-Garcia; Ge Tan; Jeanne Chèneby; Benoit Ballester; François Parcy; Albin Sandelin; Boris Lenhard; Wyeth W Wasserman; Anthony Mathelier Journal: Nucleic Acids Res Date: 2020-01-08 Impact factor: 16.971
Authors: Trevor B Doyle; Brian S Muntean; Karin F Ejendal; Michael P Hayes; Monica Soto-Velasquez; Kirill A Martemyanov; Carmen W Dessauer; Chang-Deng Hu; Val J Watts Journal: Cells Date: 2019-11-19 Impact factor: 6.600