Interpretation of ceritinib clinical trial results and future combination therapy strategies for ALK-rearranged NSCLC.

Interpretation of ceritinib clinical trial results and future combination therapy strategies for ALK-rearranged NSCLC. Expert Rev Anticancer Ther. 2019 Dec 06;:1-15 Authors: Blakely CM, Riess JW Abstract Introduction: Lung cancer is the leading cause of cancer-related deaths, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all lung cancer cases. The continued advancement of DNA sequencing technology and the discovery of multiple specific driver mutations underlying many cases of NSCLC are moving clinical intervention toward a more targeted approach. Here we focus on anaplastic lymphoma kinase (ALK), a member of the receptor tyrosine kinase family, as an oncogenic driver in NSCLC. The ALK gene is rearranged in 3-7% of NSCLCs, and targeted inhibition of ALK is a viable therapy option.Areas covered: We discuss the available treatment options for ALK-positive NSCLC with an emphasis on the second-generation ALK inhibitor ceritinib. We also discuss practical treatment strategies and possible strategies to overcome or delay resistance to ALK inhibitors.Expert opinion: With a robust treatment armamentarium for patients with ALK-positive NSCLC, emphasis has shifted to optimizing individualized treatment strategies to further enhance outcomes for these patients. PMID: 31809604 [PubMed - as supplied by publisher]
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research

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SummaryAnaplastic lymphoma kinase (ALK), which belongs to the insulin receptor tyrosine kinase superfamily, plays an important role in nervous system development. Due to chromosomal translocations, point mutations, and gene amplification, constitutively activated ALK has been implicated in a variety of human cancers, including anaplastic large-cell lymphoma (ALCL), non-small cell lung cancer, and neuroblastoma. We evaluated the anti-cancer activity of the ALK inhibitor KRCA-0008 using ALCL cell lines that express NPM (nucleophosmin)-ALK. KRCA-0008 strongly suppressed the proliferation and survival of NPM-ALK-positive ALCL ...
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research
In conclusion, Cer/Pom-PEG@GNPs can degrade intracellular ALK fusion proteins with minor off-target toxicity and can be applied in patients resistant to ALK inhibitors. As a nanodrug carrier, Cer/Pom-PEG@GNPs have the potential to enable prolonged circulation and specifically distribute drugs to tumor regions in vivo; thus, further investigation is warranted.Graphical abstract
Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research
Authors: Genova C, Rossi G, Tagliamento M, Rijavec E, Biello F, Cerbone L, Zullo L, Grossi F Abstract Introduction: The discovery of new actionable oncogenic drivers has led to the development of effective antineoplastic targeted agents in advanced non-small cell lung cancer (NSCLC). While the role of inhibitors of the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) is widely acknowledged, other oncogenic drivers can be exploited as therapeutic targets.Areas covered: Our aim is to explore the role of actionable oncogenic drivers and antineoplastic drugs exp...
Source: Expert Review of Respiratory Medicine - Category: Respiratory Medicine Tags: Expert Rev Respir Med Source Type: research
Targeted therapies are a standard of care for first-line treatment of Anaplastic lymphoma kinase (ALK)-rearranged non small cell lung cancer (NSCLC). Giving the rapid pace of drug discovery and development in thi...
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Case report Source Type: research
AbstractPurposeOur study intended to explore the association between combining18F –FDG PET/CT metabolic parameters and other clinical features and anaplastic lymphoma kinase (ALK) or c-ros oncogene 1 (ROS1) fusion in non-small-cell lung cancer (NSCLC).MethodsEight hundred and six patients with wild-type epidermal growth factor receptor (EGFR) mutation were screened for ALK or ROS1 fusion and subjected to18F –FDG PET/CT prior to treatment at our hospital. The associations between ALK or ROS1 fusion and clinical characteristics and the PET/CT parameters were analyzed. Multivariate logistic regression analysis was...
Source: European Journal of Nuclear Medicine and Molecular Imaging - Category: Nuclear Medicine Source Type: research
We report about a 67 years old man with cerebellar symptoms and a weight loss of 10 kg who was treated in our clinic. After our diagnostic work up we found a non small cell cancer and diagnosed a subacute degeneration of the cerebellum as a paraneoplastic disorder. We found a high positive titer for Anti-Tr3 antibodies while the rest of the paraneoplastic antibodies described as typically associated with the subacute degeneration of the cerebellum were negative. The Anti-Tr3 antibodies are usually found in patients with Hodgkin and less often Non-Hodgkin disease. After initiation of a tumor specific therapy and intraveno...
Source: Der Nervenarzt - Category: Neurology Authors: Tags: Nervenarzt Source Type: research
The development of targeted therapies has revolutionized the treatment of patients with lung cancer, especially non-small-cell lung cancer (NSCLC). Anaplastic lymphoma kinase (ALK) is a research hotspot of molecular targeted therapy for lung cancer. ALK tyrosine kinase inhibitors (TKIs) are highly effective for ALK-rearranged NSCLC-positive patients. These targeted therapies have significant clinical effects; however, they inevitably lead to acquired resistance. In previous studies, the histological transformation after ALK inhibitor treatment was mostly based on small-cell lung cancer (SCLC).
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
This study was undertaken to determine ICI efficacy against epidermal growth-factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)/c-ros oncogene 1 (ROS1)-mutated NSCLC patients in the real-world setting. In this retrospective, multicenter study on adults with ICI-treated EGFR-mutated or ALK- or ROS1-translated NSCLCs, we analyzed clinical characteristics and outcomes: ICI-treatment duration, and progression-free survival (PFS), objective response rate, duration of response, and overall survival (OS) from immunotherapy initiation. Fifty-one NSCLC patients (mean age, 58.0 years) were included from 20 French centers: 61%...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research
Publication date: Available online 30 December 2019Source: Seminars in Cancer BiologyAuthor(s): Biagio Ricciuti, Giuseppe Lamberti, Elisa Andrini, Carlo Genova, Andrea De Giglio, Vanessa Bianconi, Amirhossein Sahebkar, Rita Chiari, Matteo PirroAbstractWith 9.6 million deaths in 2018, cancer represents one of the most common causes of death, both in men and women. Despite recent advances in the understanding of molecular mechanisms involved in cancer development and progression, treatment options are still limited. Limitations of traditional chemotherapy include the lack of selectivity and the unfavorable safety profile. Th...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Conclusion: Concurrent treatment with WBRT and ALK-TKI may be associated with acute severe ear toxicity in patients with BMs of ALKr-NSCLC.
Source: In Vivo - Category: Research Authors: Tags: Clinical Studies Source Type: research
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