Targeted therapies for ROS1-rearranged non-small cell lung cancer.

Targeted therapies for ROS1-rearranged non-small cell lung cancer. Drugs Today (Barc). 2019 Oct;55(10):641-652 Authors: Patil T, Simons E, Mushtaq R, Pacheco JM, Doebele RC, Bowles DW Abstract ROS1 gene fusions account for approximately 1-2% of all cases of non-small cell lung cancer (NSCLC). Similarly to anaplastic lymphoma kinase (ALK)-positive NSCLC, patients with ROS1+ NSCLC tend to have minimal smoking and be of the female sex. In most cases, adenocarcinoma is the dominant histology. The ROS1 gene has homology to ALK and this structural similarity formed the basis for utilizing ALK inhibitors for ROS1+ NSCLC. On the basis of impressive progression-free survival of 19.2 months from the PROFILE 1001 trial, crizotinib obtained Food and Drug Administration (FDA) approval as first-line therapy for treatment of ROS1+ NSCLC. Since then, there has been a growing appreciation of the incidence of brain metastases in ROS1+ NSCLC and rates of central nervous system progression on crizotinib. Additionally, appreciation of novel resistance mechanisms to crizotinib has led to the development of newer tyrosine kinase inhibitors (TKIs). In this review, we highlight known and emerging TKIs for the management of ROS1+ NSCLC. PMID: 31720561 [PubMed - in process]
Source: Drugs of Today - Category: Drugs & Pharmacology Tags: Drugs Today (Barc) Source Type: research

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ConclusionIn cases of anaplastic lymphoma kinase-positive lung cancer poorly responsive to anaplastic lymphoma kinase inhibitors, re-examination of the tissue should be considered because there is a possibility of anaplastic lymphoma kinase-positive adenosquamous carcinoma.
Source: Journal of Medical Case Reports - Category: General Medicine Source Type: research
In conclusion, we showed hypermethylation of CpGs as a novel mechanism of action for DNMTi agents and identified 638 hypermethylated molecular targets (CpGs) common to decitabine and azacytidine therapy. These novel results suggest that hypermethylation of CpGs should be considered when predicting the DNMTi responses and side effects in cancer patients. Introduction DNA methyltransferase inhibitors (DNMTi) are widely used as chemical tools for hypomethylating the genome, with an aim to understand the role of DNA methylation in multiple processes (e.g., X-chromosome inactivation and DNA imprinting) and as an anti-ca...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionCrizotinib was effective and well tolerated in Chinese patients withROS1-positive advanced NSCLC in real-world clinical practice. The progression sites and patterns, as well as treatments after first disease progression on crizotinib were diverse. Crizotinib beyond progressive disease and local therapy after failure of crizotinib treatment were feasible and effective in clinical practice.
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research
Authors: Okimoto T, Tsubata Y, Hotta T, Hamaguchi M, Nakao M, Hamaguchi SI, Hamada A, Isobe T Abstract The central nervous system is a common site of relapse in patients receiving crizotinib, which is presumed to be associated with the low concentration of crizotinib in the cerebrospinal fluid (CSF). Our patient received surgical treatment for anaplastic lymphoma kinase-positive stage IIA lung adenocarcinoma. His cancer recurred with brain metastases and carcinomatous meningitis. We started whole-brain radiation therapy (WBRT) and subsequently administered crizotinib. The concentration of crizotinib on day 15 in th...
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
ConclusionsYoung patients are associated with an increased likelihood of gene mutations and can receive a better prognosis when patients harboring gene mutations are treated with EGFR-TKIs or ALK inhibitors.
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
Rationale: The treatment of non-small cell lung cancer (NSCLC) has now changed dramatically in recent years and anaplastic lymphoma receptor tyrosine kinase (ALK) inhibitors are developing rapidly. Patient concerns: Here we reported a 57-year-old ALK-positive NSCLC man with brain metastases. Diagnoses: A case of lung adenocarcinoma with brain metastases. Interventions: Crizotinib was administered orally at a dose of 250mg twice a day until the brain metastases were found. Treatment with orally administered ceritinib at a dose of 450mg/d was initiated after crizotinib treatment. Outcomes: The patient is curren...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
Abstract Brain metastasis from non-small cell lung cancer remains a challenge to physicians. It occurs in 30% of patients with advanced stage adenocarcinoma of lung and is often regarded as the ominous sign of disease progression and death. Alectinib is likely to be a promising agent, even after the failure of crizotinib and ceritinib, for patients with anaplastic lymphoma kinase (ALK) -driven non-small cell lung cancer with brain metastasis, resulting in a durable response for both intracranial and extra-cranial diseases. PMID: 28275428 [PubMed - in process]
Source: Cancer Control - Category: Cancer & Oncology Authors: Tags: Respirol Case Rep Source Type: research
Abstract Crizotinib has achieved astonishing success in advanced non‐small‐cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement. However, no real‐world studies described the clinicopathological characteristics and treatment of such patients in China. Patients were consecutively collected from Sun Yat‐sen University Cancer Center. Chi‐square test was applied to explore the relationship between ALK fusion status and metastasis sites. Kaplan–Meier methods and multivariable analyses were used to estimate progression‐free survival (PFS). A total of 291 advanced NSCLC patie...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: Original Research Source Type: research
Conclusions:Early recognition of new neurological patterns of toxicity may lead to drug discontinuation or dose adjustment preventing further neurological deterioration. A better knowledge of these toxicities will help differentiate treatment-related complications from metastatic progression.
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: P14 Neurotoxicity and neuroprotection Source Type: research
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