LTBP1-ALK: A Novel Fusion identified in malignant pleural effusions from a patient with advanced Lung Adenocarcinoma

ALK (Anaplastic lymphoma kinase) rearrangement is the second most common targetable oncogene-dirven gene in NSCLC. It is identified in approximately 3 –7% of NSCLC patients [1], and is highly sensitive to ALK tyrosine kinase inhibitors (TKIs) such as crizotinib, alectinib, ceritinib, brigatinib [2]. EML4-ALK rearrangement was firstly identified by Soda et al. in 2007 [3]. With the development of NGS, more and more novel ALK fusion partners have been identified, such as KIF5B, STRN, KLC1, TPR, HIP1, DCTN1, CMTR1, GCC2, SEC31A and so on.
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research

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Approximately 5% of non-small cell lung cancers (NSCLC) harbor an anaplastic lymphoma kinase (ALK) rearrangement. Several ALK tyrosine kinase inhibitors (TKI) have demonstrated their efficacy as first line treatment for advanced ALK-positive NSCLC (1). However, patients treated with these drugs eventually develop acquired TKI resistance and tumor progression, and the question of the therapeutic options beyond ALK TKI resistance remains a critical issue. Since 2014, immune checkpoint inhibitors (ICI) have become a major treatment in advanced NSCLC.
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
The frequency of anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) is approximately 3% to 5% [1], and the administration of ALK tyrosine kinase inhibitors has achieved impressive outcomes. Apart from EML4 –ALK, various ALK fusion partner genes have recently been identified [2]. In this case, we report a novel PNPT1 (polyribonucleotide nucleotidyl transferase 1)–ALK fusion responding to crizotinib in a patient with lung adenocarcinoma.
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
Chromosome rearrangement involving anaplastic lymphoma kinase (ALK) has been identified in 3-5% NSCLC patients1, and ALK rearrangements have been defined as a molecular subset of NSCLC. Since the first report of echinoderm microtubule-associated like 4 (EML4) –ALK fusion in 20072, more than 90 fusion partners of the ALK gene have been identified in NSCLC3. PROFILE 1014 laid the first-line treatment status of crizotinib in patients with advanced ALK fusion-positive NSCLC4. However, emerging data suggest that clinical outcomes of crizotinib are vary from type to type of ALK fusion types.
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
Conclusion: Among this large cohort, our center seems to follow the global trend with increasing incidence of ADC. EGFR mutation positivity was similar to existing reports, while higher ALK positivity was detected. A characteristic phenotype of never-smokers with lung cancer was elucidated which demonstrated better survival.
Source: Lung India - Category: Respiratory Medicine Authors: Source Type: research
Conclusion NGS assay revealed a distinctive genetic profile in younger patients with adenocarcinoma. High frequency of concurrent EGFR/TP53 mutations was found in the younger patients, which especially warranted personalized treatment in this population. DOI: 10.3779/j.issn.1009-3419.2020.101.17
Source: Chinese Journal of Lung Cancer - Category: Cancer & Oncology Source Type: research
Lung cancer remains the leading cause of cancer death worldwide [1]. A majority of lung cancers can be classified as non-small cell lung cancer (NSCLC), the largest group of which are adenocarcinomas. The management of metastatic NSCLC (mNSCLC) adenocarcinoma depends on the presence or absence of an oncogenic driver mutation. The list of targetable mutations in oncogene driven mNSCLC now includes epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS1, KRAS-G12C, NTRK, BRAF, MET, RET, PIK3CA, MEK, ERBB2 and the list is expected to grow [2 –4].
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
AbstractAnaplastic lymphoma kinase (ALK) rearrangements have been reported in 5% to 6% of non ‐small cell lung cancer (NSCLC) patients. However, the concurrent existence of twoALK fusions within the same patient have rarely previously been reported. Moreover, considering the diversities ofALK mutations, it is necessary to evaluate the response of both double and new types ofALK fusions to ALK ‐tyrosine kinase inhibitors (ALK‐TKIs). Here, we report a case of a 64‐year‐old Chinese woman who was diagnosed with lung adenocarcinoma (ADC) who concurrently harbored two types ofALK‐rearrangements, including an unreport...
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: CASE REPORT Source Type: research
Rearrangements in ROS1 oncogene, reported in 1 –2% of patients with non-small cell lung cancer (NSCLC), define a separate molecular sub-group of NSCLC [1]. Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor with the ability to cross the blood-brain barrier and have sub-nanomolar enzymatic efficacy in ta rgeting rearrangements in ALK and ROS1 [2]. ROS1 G2032R has been reported as the most commonly acquired mutation that mediates resistance to crizotinib therapy [3–5]; however, mechanisms that mediate lorlatinib resistance among patients with ROS1 rearrangement are rarely reported.
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
Rearrangements in ROS1 oncogene, reported in 1 –2% of patients with non-small cell lung cancer (NSCLC), define a separate molecular sub-group of NSCLC [1]. Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor with the ability to cross the blood-brain barrier and have sub-nanomolar enzymatic efficacy in ta rgeting rearrangements in ALK and ROS1 [2]. ROS1 G2032R has been reported as the most commonly acquired mutation that mediates resistance to crizotinib therapy [3–5]; however, mechanisms that mediate lorlatinib resistance among patients with ROS1 rearrangement are rarely reported.
Source: Lung Cancer - Category: Cancer & Oncology Authors: Source Type: research
ConclusionsThis study indicated that CT ‐707 is clinically effective as a new antitumor drug for Chinese lung adenocarcinoma patients with ALK rearrangement. It is safe and reliable and the dose‐expansion phase recruitment has started.
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
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