ABSTRACT
Rearranged during transfection (RET) fusions are found in 0.7% to 2% of non-small cell lung cancer (NSCLC). Fusions between RET gene and other domains represent the distinct biological and clinicopathological subtypes of NSCLC. Recent years have witnessed the remarkable advancement of RET fusion-positive advanced NSCLC therapy. Conventional chemotherapy produced moderate clinical benefits. Prior to the introduction of targeted therapy or in the context of unavailability, platinum-based systemic regimens are initial therapy options. Immunotherapy predicted minimal response in the presence of RET fusions while currently available data have been scarce, and the single-agent immunotherapy or in combination with chemotherapy regimens are not recommended as initial systemic therapy in this population. The repurpose of multi-target kinase inhibitors in patients with RET fusion-positive NSCLC showed encouraging therapeutic activity, with only cabozantinib and vandetanib being recommended as initial or subsequent options under certain circumstances. However, there are still unmet clinical needs. Pralsetinib and selpercatinib have been developed as tyrosine kinase inhibitors (TKI) selectively targeting RET variation of fusions or mutations, and both agents significantly improved the prognosis of patients with RET fusion-positive NSCLC. Pralsetinib and selpercatinib have been established as preferred first-line therapy or subsequent therapy options. As observed with other TKIs treatment, resistance has also been associated with RET targeted inhibition, and the acquired resistance eventually affect the long-term therapeutic effectiveness, leading to limited subsequent treatment options. Therefore, it is essential to identify resistance mechanisms to TKI in RET fusion-positive advanced NSCLC to help reveal and establish new strategies to overcome resistance. Here, we review the advances in the treatment of RET fusion-positive advanced NSCLC. .
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Mutation , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-ret/geneticsABSTRACT
<p><b>BACKGROUND</b>To explore the experience of gefitinib molecular target therapy for Chinese patients with non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>The unpublished data of gefitinib for advanced NSCLC in 7 hospitals were collected. The detailed data from Guangdong Provincial People's Hospital were analyzed.</p><p><b>RESULTS</b>A total of 282 patients with advanced NSCLC was treated with gefitinib from July 2001 to December 2003. Response rate was 22.2%-47.7%, disease control rate 62.6%-81.8%. No severe side effects were surveyed.</p><p><b>CONCLUSIONS</b>Gefitinib can be used safely and effectively in Chinese patients with advanced NSCLC.</p>
ABSTRACT
Objective To study the genes which simultaneously participate in different carcinogenesis progression in lung adenocarcinoma for biomarkers identification. Methods 10 lung adenocarcinoma samples including pathologic stage Ⅰ,Ⅱ,Ⅲ were chosen for experiment and their matched normal tissues for control. After hybridization on 20 slides of microarray with 13824 genes, we analyze the expression profiles combined with pathologic stage and clinical prognosis by data mining. The genes differentially coexpressed in different stage and different prognosis samples were the target. Results 119 genes were identified. Among these targets, 26 genes have known to be related to lung cancer, 46 genes were unreported and 47 gene were new. Conclusions The 119 genes were very important during cancer occurrence and development and were the candidate biomarkers in lung adenocarcinoma.