PDF(Pubmed)
Abstract：
UNASSIGNED: Oncogenic NTRK fusions have been found in multiple cancer types affecting adults and/or children, including rare tumors with pathognomonic fusions and common cancers in which fusions are rare. The tropomyosin receptor kinase inhibitors (TRKi) larotrectinib and entrectinib are among the first agents with tissue agnostic FDA approvals for cancer treatment, and additional TRKi are undergoing development. As experience with TRKi grow, novel mechanisms of resistance and on/off target side effects have become increasingly important considerations.
UNASSIGNED: Authors reviewed literature published through July 2023 on platforms such as PubMed, clinicaltrials.gov, and manufacturer/FDA drug labels, focusing on the development of TRKi, native functions of TRK, phenotype of congenital TRK aberrancies, efficacy, and safety profile of TRKi in clinical trials and investigator reports, and on/off target adverse effects associated with TRKi (Appendix A).
UNASSIGNED: TRKi have histology-agnostic activity against tumors with NTRK gene fusions. TRKi are generally well tolerated with a side effect profile that compares favorably to cytotoxic chemotherapy. There are numerous ongoing studies investigating TRKi as frontline, adjuvant, and salvage therapy. It will be critical to continue to gather long-term safety data on the use of these agents, particularly in children.
UNASSIGNED: Authors reviewed literature published through July 2023 on platforms such as PubMed, clinicaltrials.gov, and manufacturer/FDA drug labels, focusing on the development of TRKi, native functions of TRK, phenotype of congenital TRK aberrancies, efficacy, and safety profile of TRKi in clinical trials and investigator reports, and on/off target adverse effects associated with TRKi (Appendix A).
UNASSIGNED: TRKi have histology-agnostic activity against tumors with NTRK gene fusions. TRKi are generally well tolerated with a side effect profile that compares favorably to cytotoxic chemotherapy. There are numerous ongoing studies investigating TRKi as frontline, adjuvant, and salvage therapy. It will be critical to continue to gather long-term safety data on the use of these agents, particularly in children.
摘要：
■在影响成人和/或儿童的多种癌症类型中发现了致癌NTRK融合，包括具有病理信号融合的罕见肿瘤和融合罕见的常见癌症。原肌球蛋白受体激酶抑制剂（TRKi）larotrectinib和entrectinib是首批获得FDA批准的癌症治疗药物之一。和其他TRKi正在开发中。随着TRKi经验的增长，新的耐药机制和开/关靶标副作用已成为越来越重要的考虑因素。
■作者回顾了截至2023年7月在PubMed等平台上发表的文献，clinicaltrials.gov,和制造商/FDA药物标签，专注于TRKi的发展，TRK的本机函数，先天性TRK异常的表型，TRKi在临床试验和研究者报告中的疗效和安全性，以及与TRKi相关的开/关目标不良反应。
■TRKi对NTRK基因融合的肿瘤具有组织学不可知的活性。TRKi通常具有良好的耐受性,具有与细胞毒性化疗相比有利的副作用特征。有许多正在进行的研究以TRKi为前线，佐剂,和抢救疗法。继续收集有关这些药物使用的长期安全数据至关重要。特别是在儿童中。
■作者回顾了截至2023年7月在PubMed等平台上发表的文献，clinicaltrials.gov,和制造商/FDA药物标签，专注于TRKi的发展，TRK的本机函数，先天性TRK异常的表型，TRKi在临床试验和研究者报告中的疗效和安全性，以及与TRKi相关的开/关目标不良反应。
■TRKi对NTRK基因融合的肿瘤具有组织学不可知的活性。TRKi通常具有良好的耐受性,具有与细胞毒性化疗相比有利的副作用特征。有许多正在进行的研究以TRKi为前线，佐剂,和抢救疗法。继续收集有关这些药物使用的长期安全数据至关重要。特别是在儿童中。
