In this open-label, multicentre, phase 2 trial (LURET), patients with advanced RET-rearranged NSCLC continuously received 300 mg of oral vandetanib daily.
CONCLUSIONS The results of this research indicate that the metastases of non-small cell lung cancer can predict RET rearrangement of the primary tumor tissue in the majority of cases.
Systemic and CNS activity of the RET inhibitor vandetanib combined with the mTOR inhibitor everolimus in KIF5B-RET re-arranged non-small cell lung cancer with brain metastases.
Clinical trials are underway to investigate the therapeutic effects of RET tyrosine kinase inhibitors, such as vandetanib (ZD6474) and cabozantinib (XL184), in patients with RET fusion-positive non-small-cell lung cancer.
Cabozantinib, an orally bioavailable tyrosine kinase inhibitor with activity against MET, vascular endothelial growth factor receptor 2, AXL, ROS1, and RET was assessed in patients with non-small-cell lung carcinoma (NSCLC) as part of a phase II randomized discontinuation trial with cohorts from 9 tumor types.
Using a transcript-based method, we designed a combination of 3' overexpression and fusion-specific detection strategies to detect ALK, ROS1 and RET fusion transcripts in NSCLC tumors.
While RET TK inhibitors (TKIs) are used to treat thyroid cancer and are in clinical trials for RET fusion-positive non-small cell lung cancer, the impact of mutations in the RET kinase domain on drug sensitivity is largely uncharacterized.
Anaplastic lymphoma receptor tyrosine kinase (<i>ALK</i>), ROS proto-oncogene 1, receptor tyrosine kinase (<i>ROS1</i>), and ret proto-oncogene (<i>RET</i>) fusions are present in 5%-7% of patients with advanced non-small-cell lung cancer (NSCLC); their accurate identification is critical to guide targeted therapies.
Our case expands the spectrum of RET fusion partners and supports broad molecular profiling in non-small cell lung cancer optimizing patient therapeutic options.
We describe the implementation of an Illumina TruSight Tumor (TST) clinical NGS diagnostic framework and parallel validation of a NanoString RNA-based ALK, RET, and ROS1 gene fusion assay for combined analysis of treatment predictive alterations in non-small cell lung cancer (NSCLC) in a regional healthcare region of Sweden (Scandinavia).
In first-in-human testing, BLU-667 significantly inhibited RET signaling and induced durable clinical responses in patients with <i>RET</i>-altered NSCLC and MTC without notable off-target toxicity, providing clinical validation for selective RET targeting.<b>Significance:</b> Patients with <i>RET</i>-driven cancers derive limited benefit from available MKIs.
Advanced RET-rearranged NSCLC manifested as a relatively small and peripherally located solid primary lesion with or without small solitary lymphadenopathy.
A new RET fusion gene has been recently described in a subset of non-small cell lung cancer (NSCLC) identified by specific clinico-pathologic characteristics.
Recent clinical trials for RET fusion-positive NSCLC using vandetanib or cabozantinib demonstrated positive clinical response and considerable differential activities for RET inhibitors among fusion partners.
Detection of Gene Rearrangements in Circulating Tumor Cells: Examples of ALK-, ROS1-, RET-Rearrangements in Non-Small-Cell Lung Cancer and ERG-Rearrangements in Prostate Cancer.
Emerging clinical studies have demonstrated that patients with RET-rearranged NSCLC may also benefit from existing RET TKIs, including cabozantinib and vandetanib.