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Abnormal alternative splicing promotes tumor resistance in targeted therapy and immunotherapy
Authors:Kun Deng  Jingwei Yao  Jialu Huang  Yubo Ding  Jianhong Zuo
Affiliation:aThe Laboratory of translational medicine, Hengyang Medical School, University of South China, 28 Changsheng Road, Hengyang, Hunan 421001, P R China;bThe Affiliated Nanhua Hospital of University of South China, Hengyang, Hunan 421002, P R China;cClinical Laboratory, The Third Affiliated Hospital of University of South China, Hengyang, Hunan 421900, China
Abstract:Abnormally alternative splicing events are common hallmark of diverse types of cancers. Splicing variants with aberrant functions play an important role in cancer development. Most importantly, a growing body of evidence has supported that alternative splicing might play a significant role in the therapeutic resistance of tumors. Targeted therapy and immunotherapy are the future directions of tumor therapy; however, the loss of antigen targets on the tumor cells surface and alterations in drug efficacy have resulted in the failure of targeted therapy and immunotherapy. Interestingly, abnormal alternative splicing, as a strategy to regulate gene expression, is reportedly involved in the reprogramming of cell signaling pathways and epitopes on the tumor cell surface by changing splicing patterns of genes, thus rendering tumors resisted to targeted therapy and immunotherapy. Accordingly, increased knowledge regarding abnormal alternative splicing in tumors may help predict therapeutic resistance during targeted therapy and immunotherapy and lead to novel therapeutic approaches in cancer. Herein, we provide a brief synopsis of abnormal alternative splicing events in cancer progression and therapeutic resistance.
Keywords:Alternative splicing   Cancer   Targeted therapy   Immunotherapy   Resistance
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