Targeted degradation of anaplastic lymphoma kinase by gold nanoparticle-based multi-headed Proteolysis Targeting Chimeras

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

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We describe outcomes of real-life patients according to the treatment strategy received.PatientsWe retrospectively collected 290 ALK rearranged advanced NSCLC diagnosed between 2011 and 2017 in 23 Italian institutions.ResultsAfter a median follow-up of 26  months, PFS for crizotinib and a new generation ALKis were 9.4 [CI 95% 7.9–11.2] and 11.1 months [CI 95% 9.2–13.8], respectively, while TTF were 10.2 [CI 95% 8.5–12.6] and 11.9 months [CI 95% 9.7–17.4], respectively, being consistent across the different settings. The composed outcomes ( the sum of PFS or TTF) in patients treated wi...
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
Objectives: To identify a computed tomography (CT)-based radiomic signature for predicting progression-free survival (PFS) in stage IV anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitor (TKI) crizotinib.Materials and Methods: This retrospective proof-of-concept study included a cohort of 63 stage IV ALK-positive NSCLC patients who had received TKI crizotinib therapy for model construction and validation. Another independent cohort including 105 stage IV EGFR-positive NSCLC patients was also used for external validation in EGFR-TKI treatment. We initi...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSION: The maximum tolerated dose was not determined because slow accrual resulted in early study termination. PMID: 32048771 [PubMed - as supplied by publisher]
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
We present a unique and successful case of a young patient with primary refractory ALK-positive LBCL who received salvage chemotherapy plus brigatinib followed by allogeneic stem cell transplantation.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 339 Source Type: research
Authors: Huang M, Tian Y, He M, Liu J, Ren L, Gong Y, Peng F, Wang Y, Ding Z, Wang J, Zhu J, Xu Y, Liu Y, Li L, Lu Y Abstract Aim: To assess the cost-effectiveness of crizotinib verses platinum-based doublet chemotherapy as the first-line treatment for Anaplastic Lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) in the real-world setting. Methods: Data from 163 advanced ALK positive NSCLC patients were collected from West China Hospital, Sichuan University (Chengdu, China). They were categorized into two groups as treated with crizotinib (n = 83) or chemotherapy (n = 80) as a fir...
Source: Journal of Comparative Effectiveness Research - Category: General Medicine Tags: J Comp Eff Res Source Type: research
CONCLUSION: Long non-coding RNA DLEU1 is likely to represent an available biomarker or a potential therapeutic target in multiple tumors. PMID: 31969095 [PubMed - as supplied by publisher]
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
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
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
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