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ROS1 - DOAJ

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Last Updated: 27 July 2022

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A Phase 2 Study of Lorlatinib in Patients With ROS1-Rearranged Lung Cancer With Brain-Only Progression on Crizotinib

Introduction: The central nervous system is a common site of progression in patients with RS1-rearranged lung cancer receiving crizotinib. We performed a phase 2 study to determine the intracranial safety of lorlatinib in patients with ROS1-rearranged lung cancer who experienced CNS-only progression on crizotinib. Patients with metastatic ROS1-rearranged lung cancer with CNS-only progression on crizotinib were given lorlatinib 100 mg daily. Seven patients experienced disease progression, including five patients with CNS relapse, with median follow-up of 22 months. The ROS1 G2032R, ROS1 L2086F, and CCDC6-RET fusion plus ROS1 G2032R were discovered in a biological study of plasma or tissue from patients with extracranial change on lorlatinib. There were 11 patients who required dose reduction, including one patient who stopped treatment for grade 3 edema. Lorlatinib produced durable intracranial responses in patients with ROS1-rearranged NSCLC and preceding isolated CNS progression on crizotinib.

Source link: https://doi.org/10.1016/j.jtocrr.2022.100347


Discovery of a novel ALK/ROS1/FAK inhibitor, APG-2449, in preclinical non-small cell lung cancer and ovarian cancer models

To determine the therapeutic efficacy of monotherapy or a drug combination in preclinical models of solid tumors, water-soluble tetrazolium salt viability assay and xenograft tumorigenicity were used. APG-2449 sensitizes ovarian xenograft tumor tumors to paclitaxel by lowering CD44+ and aldehyde dehydrogenase 1-positive stem cell populations, including ovarian tumors that are sensitive to carboplatin. TKI-induced tumor growth inhibition is exacerbated by APG-2449's mutation in epidermal growth factor receptor-mutated NSCLC xenograft models, while the ternary combination of APG-2449 with EGFR and mitogen-regulated extracellular signal-regulated kinase inhibitors overcomes osimertinib resistance, despite osim resistance. Conclusions based on these results: When administered alone or in combination with other therapies, APG-2449 demonstrates potent and long-lived antitumor growth in human NSCLC and ovarian tumor models. A phase 1 clinical trial has begun to determine the safety and preliminary efficacy of APG-2449 in patients with advanced solid tumors, including ALK + NSCLC refractory to earlier-generation ALK inhibitors.

Source link: https://doi.org/10.1186/s12885-022-09799-4


The performance of ensemble-based free energy protocols in computing binding affinities to ROS1 kinase

Abstract: A key target in drug discovery is to improve binding affinities for substances to their target protein. To determine the binding free energies, we use ESMACS and TIES protocols. The predicted binding free energies from ESMACS simulations show good correlations with experimental results for subsets of the compounds. TIES and ESMACS are examples of consistent, free energy difference between TIES and ESMACS.

Source link: https://doi.org/10.1038/s41598-022-13319-6


Lack of ROS1 Gene Rearrangement in Glioblastoma Multiforme.

Glioblastoma multiforme is the most common brain tumor, and prognosis is poor. In this pilot study, we aimed to determine the prevalence of ROS1 rearrangement in GBM patient tissues in order to find new biomarkers for therapeutic use. By anti-ROS immunohistochemistry and ROS1 break-apart fluorescent in situ hybridization assays, 109 patients with GBM were tested for ROS1 rearrangement by anti-ROS immunohistochemistry and paraffin-embedded tissue sections from 109 patients with GBM. ROS1 rearrangement was not found in GBM patients, so it is difficult to measure ROS1 rearrangement as a new molecular subset in GBM patients for now.

Source link: https://doi.org/10.1371/journal.pone.0137678


G–CSF–producing left lung squamous cell carcinoma positive for ROS1 rearrangements completely resected after neoadjuvant radiation chemotherapy: A case report

Most patients with Gu2013CSF•u2013producing tumors have an aggressive clinical course and poor prognosis, with neutrophilia without infection. Following neoadjuvant radiation therapy, left lower lobectomy, and left upper lobectomy partial resection were performed, a left upper lobectomy was performed. This is the first reported case of Gu2013cSF-u2013-producing lung cancer with ROS1 rearrangements, according to our knowledge, and complete resection was performed after neoadjuvant radiation chemotherapy.

Source link: https://doi.org/10.1016/j.rmcr.2022.101697


ALK, ROS1 and EGFR status of lung cancers in the Aegean Region of Turkey

Background/Aims: While targeted therapies are promising in the treatment of lung cancer, it is important to understand the genetic variations in tumors. ALK, ROS1, and epidermal growth factor receptor genes were among the samples' variation rates, respectively, at 3. 5%, 0. 4, and 11. 2%. In young patients and females, ALK rearrangements were mainly observed. Females were also more likely to be affected by EGFR variations, especially from the exon 19 deletion. Exon 21 L858R mutations were more prevalent in males than in women.

Source link: https://doi.org/10.4103/IJPM.IJPM_1129_20


Pre‐ and post‐treatment blood‐based genomic landscape of patients with ROS1 or NTRK fusion‐positive solid tumours treated with entrectinib

We investigated the genomic landscape pre-u2010 and post-u2010entrectinib therapy to determine patients with NTRK/u2010fp or ROS1p tumors and assessed the genomic landscape before and after u2010entrectinib therapy. In both cohorts, the desired response rate for CTA+ F1L CDx+ patients was 72. 2%. F1L CDx is a clinically valid alternative to tissue-u2010 based testing to identify patients who may benefit from entrectinib and those with acquired resistance mutations associated with disease progression, according to the author.

Source link: https://doi.org/10.1002/1878-0261.13214


Multiple Brain Metastases in a Patient with ROS1 Fusion-Positive Lung Adenocarcinoma as a Disease Flare due to Crizotinib Cessation Caused by Disseminated Aseptic Inflammation from Crizotinib-Associated Renal Cysts: A Case Report

Rapid tumor formation after the cessation of molecularly targeted drugs, known as the u201disease flare, may occur and influence lung cancer's prognosis. We review a disease flare in a patient with ROS1 fusion-positive lung adenocarcinoma herein. A 60-year-old female was diagnosed with stage IVA ROS1 fusion-positive lung adenocarcinoma by bronchoscopy. Although crizotinib, a ROS1 kinase inhibitor, had partial responses, a mass lesion developed in the patient's right kidney 12 months after starting crizotinib, which was described pathologically as crizotinib-associated renal cysts, as crizotinib-associated renal cysts. Given that the readministration of crizotinib regularly caused CARC-like aseptic inflammation that appeared to be disseminated around the surgical site, crisisotinib therapy had to be suspended. In a patient with ROS1 fusion-positive lung adenocarcinoma, this is the first report of a disease flare since crizotinib withdrawal due to CARCs. Disease flare in the brain could be reduced by switching to drugs that penetrate the blood-brain barrier.

Source link: https://doi.org/10.1159/000523737


Rare MYH9-ROS1 Fusion Gene-Positive Lung Adenocarcinoma Showing Response to Entrectinib Treatment: A Case Study

The c-ros oncogene 1 fusion gene is a rare genetic mutation that has been present in nearly 11% of lung adenocarcinomas. MYH9-ROS1 fusion gene-positive lung adenocarcinoma, a rare ROS1 fusion gene. After a thorough examination, the patient was found with advanced primary lung adenocarcinoma in her 40s. There were no driver gene mutations identified by endobronchial ultrasound-guided transbronchial needle aspiration, including the ROS1 fusion gene. This is the first review of entrectinib's safety against lung adenocarcinoma with the uncommon MYH9-ROS1 fusion gene.

Source link: https://doi.org/10.1159/000524071


Expression and Prognostic Significance of c-Myc, ALK, ROS1, BRAF, and PD-L1 Among Patients With Non-Small Cell Lung Cancer

Background: Non-small cell lung cancer is the leading cause of cancer death worldwide, and for which research into molecular prognostic factors is critical. Of these, 66 matched specimens of normal respiratory epithelial and tumor tissue from patients with stages I-III, who underwent surgical resection, and 58 NSCLC specimens from stage IV patients were included in this study. Results: Positive expression of c-Myc was found in 12 specimens of NSCLC tissue, including none of the normal respiratory epithelial tissue, which had no c-Myc antibodies. 7 patients had PD-L1-positive staining in 1%-49% tumor cells, and 7 patients had PD-L1-positive staining in u2a7e50% tumor cells, with 28 out of 66 NSCLC patients showing PD-L1-positive staining on 1%-49% tumor cells, and 7 patients had PD-L1-positive staining in u2a7e50% tumor cells. Adenocarcinoma patient was found to have ROS1 rearrangement. Patients with no c-Myc and PD-L1 expression had a better prognosis than those subgroups.

Source link: https://doi.org/10.1177/11795549221092747

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions