Here, we report a novel <i>VKORC1L1-ALK</i> fusion and an ALKT1151K resistance mutation detected in a lung cancer patient who had been on crizotinib for over 8 years.
The increasing death rates related to anaplastic lymphoma kinase (ALK)-positive lung cancer culminated in a significant interest in the discovery of novel inhibitors for ALK.
An increasing number of retrospective studies suggest that molecular-targeted therapy, such as EGFR and ALK inhibitors in lung cancer, trastuzumab in HER2+ breast cancer, and BRAF inhibitors in melanoma, may be effective as part of the multidisciplinary management of LM.
The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional effort to identify and treat oncogenic driver events in patients with lung adenocarcinomas.<b>Experimental Design:</b> Sixteen U.S. institutions enrolled 1,367 patients with lung cancer in LCMC2; 904 were deemed eligible and had at least one of 14 cancer-related genes profiled using validated methods including genotyping, massively parallel sequencing, and IHC.<b>Results:</b> The use of targeted therapies in patients with <i>EGFR, ERBB2,</i> or <i>BRAF</i> p.V600E mutations, <i>ALK, ROS1</i>, or <i>RET</i> rearrangements, or <i>MET</i> amplification was associated with a survival increment of 1.5 years compared with those with such mutations not receiving targeted therapy, and 1.0 year compared with those lacking a targetable driver.
Since then, a number of novel, small-molecule inhibitors directed against the ALK receptor have demonstrated superiority over standard chemotherapies in the treatment of ALK rearrangement-positive lung cancer.
Our findings indicate that enhancer remodeling and altered expression of miRNAs play key roles in cancer drug resistance and suggest that strategies targeting epigenetic pathways represent a potentially effective method for overcoming acquired resistance to cancer therapy.<b>Significance:</b> Epigenetic deregulation drives acquired resistance to ALK inhibitors in ALK-positive lung cancer.<i></i>.
Taken together, our results indicate that simultaneous inhibition of ALK and vascular endothelial growth factor R2 by the combination of alectinib with apatinib may be useful for controlling progression of EML4-ALK fusion gene lung cancer by reversing ALK-TKI resistance and inhibiting angiogenesis.
Novel compounds for epidermal growth factor receptor-dependent and anaplastic lymphoma kinase-dependent lung cancer have demonstrated blood-brain barrier permeability and have led to important improvements in central nervous system outcomes.
Small-molecule inhibitors of Anaplastic Lymphoma Kinase (ALK) approved in ALK fusion-positive lung cancer are currently undergoing clinical assessment in patients with ALK-mutant NB.
Totally, 4622 advanced NSCLC patients from two institutes (3762 patients at the Guangdong Lung Cancer Institute from January 2011 to December 2016 and 860 cases at the Perking Cancer Hospital from January 2015 to December 2016) were screened for ALK rearrangement with any method of IHC, RACE-coupled PCR or FISH.
Herein, we report a case of a lung cancer patient with ALK rearrangement who experienced brain, leptomeningeal, and intradural extramedullary spinal cord metastases after developing resistance to crizotinib.
Median OS of EGFR-mutated or ALK-rearranged lung cancer was 78.6 months in PD-L1 positive group and 93.4 months in PD-L1 negative group (HR 0.47, 95%CI 0.23-0.76, P = 0.005).
Identification of circulating tumor cells with EML4-ALK translocation using fluorescence <i>in situ</i> hybridization in advanced ALK-positive patients with lung cancer.
The identification of anaplastic lymphoma kinase (<i>ALK</i>), an oncogenetic driver mutation, in lung cancer has paved the way for a new era in the treatment of non-small cell lung cancer (NSCLC).
Surgery, chemotherapy, and radiotherapy have been the standard treatment for lung cancer, and targeted molecular therapy has greatly improved the clinical course of patients with non-small-cell lung cancer (NSCLC) harboring driver mutations, such as in epidermal growth factor receptor and anaplastic lymphoma kinase genes.
ALK gene rearrangement has been observed in 3%-5% of non-small-cell lung cancers, and multiple ALK inhibitors have been developed for the treatment of ALK-positive lung cancer.