scholarly journals Tailored Therapy in Lung Cancer

2013 ◽  
Vol 20 (5) ◽  
pp. 367-368 ◽  
Author(s):  
George Rakovich ◽  
Lise Tremblay
Keyword(s):  
Lung Cancer ◽  
Current Practice ◽  
Kinase Inhibitors ◽  
Relevant Literature ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tailored Therapy ◽  
Lung Cancers ◽  
Tumour Vaccines ◽  
Active Investigation

Historically, all non-small cell lung cancers were essentially grouped together and considered to be a single disease. However, it is now recognized that non-small cell lung cancer actually comprises a genetically diverse group of tumours. This, in turn, affords a new opportunity for the development of effective treatments tailored to individual tumours and patients. Advances in molecular biology have made possible the development of drugs against specific molecular targets on cancer cells, most notably the tyrosine kinase inhibitors. The relevant literature and current practice guidelines are discussed. In addition, other related areas of active investigation, including tumour vaccines and pharmacogenetics, are briefly reviewed.

scholarly journals Biomarkers for ALK and ROS1 in Lung Cancer: Immunohistochemistry and Fluorescent In Situ Hybridization

2018 ◽  
Vol 142 (8) ◽  
pp. 922-928 ◽  
Author(s):  
Peter P. Luk ◽  
Christina I. Selinger ◽  
Annabelle Mahar ◽  
Wendy A. Cooper
Keyword(s):  
Lung Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Kinase Inhibitors ◽  
Screening Method ◽  
Genetic Alterations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancers

Context.— A small proportion of non–small cell lung cancers harbor rearrangements of ALK or ROS1 genes, and these tumors are sensitive to targeted tyrosine kinase inhibitors. It is crucial for pathologists to accurately identify tumors with these genetic alterations to enable patients to access optimal treatments and avoid unnecessary side effects of less effective agents. Although a number of different techniques can be used to identify ALK- and ROS1-rearranged lung cancers, immunohistochemistry and fluorescence in situ hybridization are the mainstays. Objective.— To review the role of immunohistochemistry in assessment of ALK and ROS1 rearrangements in lung cancer, focusing on practical issues in comparison with other modalities such as fluorescence in situ hybridization. Data Sources.— This manuscript reviews the current literature on ALK and ROS1 detection using immunohistochemistry and fluorescence in situ hybridization as well as current recommendations. Conclusions.— Although fluorescence in situ hybridization remains the gold standard for detecting ALK and ROS1 rearrangement in non–small cell lung cancer, immunohistochemistry plays an important role and can be an effective screening method for detection of these genetic alterations, or a diagnostic test in the setting of ALK.

scholarly journals Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3293
Author(s):  
Alberto D’Angelo ◽  
Navid Sobhani ◽  
Robert Chapman ◽  
Stefan Bagby ◽  
Carlotta Bortoletti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Resistance Mechanisms ◽  
Small Cell ◽  
Great Effort ◽  
Significant Activity ◽  
Small Cell Lung ◽  
Lung Cancers

The treatment of patients affected by non-small cell lung cancer (NSCLC) has been revolutionised by the discovery of druggable mutations. ROS1 (c-ros oncogene) is one gene with druggable mutations in NSCLC. ROS1 is currently targeted by several specific tyrosine kinase inhibitors (TKIs), but only two of these, crizotinib and entrectinib, have received Food and Drug Administration (FDA) approval. Crizotinib is a low molecular weight, orally available TKI that inhibits ROS1, MET and ALK and is considered the gold standard first-line treatment with demonstrated significant activity for lung cancers harbouring ROS1 gene rearrangements. However, crizotinib resistance often occurs, making the treatment of ROS1-positive lung cancers more challenging. A great effort has been undertaken to identify a new generation or ROS1 inhibitors. In this review, we briefly introduce the biology and role of ROS1 in lung cancer and discuss the underlying acquired mechanisms of resistance to crizotinib and the promising new agents able to overcome resistance mechanisms and offer alternative efficient therapies.

scholarly journals Immunotherapy for ALK-Rearranged Non-Small Cell Lung Cancer: Challenges Inform Promising Approaches

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1476
Author(s):  
Kamya Sankar ◽  
Sunitha Nagrath ◽  
Nithya Ramnath
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
Anaplastic Lymphoma

Rearrangements in the Anaplastic Lymphoma Kinase (ALK) gene have been implicated in 5–6% of all non-small cell lung cancers. ALK-rearranged non-small cell lung cancers are sensitive to ALK-directed tyrosine kinase inhibitors, but generally resistant to single-agent immune checkpoint inhibitors. Here, we aim to describe the mechanisms of ALK aberrations in non-small cell lung cancer by which an immunosuppressed tumor microenvironment is created, leading to host immune evasion. We report pre-clinical and clinical studies evaluating novel immunotherapeutic approaches and describe the promises and challenges of incorporating immune-based treatments for ALK-rearranged non-small cell lung cancer.

Exhaustive Review on Lung Cancers: Novel Technologies

2019 ◽  
Vol 15 (9) ◽  
pp. 873-883
Author(s):  
Sajad Khan ◽  
Shahid Ali ◽  
Muhammad
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Therapy ◽  
Small Cell ◽  
X Rays ◽  
Small Cell Lung ◽  
Microscopic Appearance ◽  
Lung Cancers ◽  
Novel Technologies

Background:Lung cancers or (Bronchogenic-Carcinomas) are the disease in certain parts of the lungs in which irresistible multiplication of abnormal cells leads to the inception of a tumor. Lung cancers consisting of two substantial forms based on the microscopic appearance of tumor cells are: Non-Small-Cell-Lung-Cancer (NSCLC) (80 to 85%) and Small-Cell-Lung-Cancer (SCLC) (15 to 20%).Discussion:Lung cancers are existing luxuriantly across the globe and the most prominent cause of death in advanced countries (USA & UK). There are many causes of lung cancers in which the utmost imperative aspect is the cigarette smoking. During the early stage, there is no perspicuous sign/symptoms but later many symptoms emerge in the infected individual such as insomnia, headache, pain, loss of appetite, fatigue, coughing etc. Lung cancers can be diagnosed in many ways, such as history, physical examination, chest X-rays and biopsy. However, after the diagnosis and confirmation of lung carcinoma, various treatment approaches are existing for curing of cancer in different stages such as surgery, radiation therapy, chemotherapy, and immune therapy. Currently, novel techniques merged that revealed advancements in detection and curing of lung cancer in which mainly includes: microarray analysis, gene expression profiling.Conclusion:Consequently, the purpose of the current analysis is to specify and epitomize the novel literature pertaining to the development of cancerous cells in different parts of the lung, various preeminent approaches of prevention, efficient diagnostic procedure, and treatments along with novel technologies for inhibition of cancerous cell growth in advance stages.

scholarly journals Circulating tumor cell copy-number heterogeneity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Marianne Oulhen ◽  
Patrycja Pawlikowska ◽  
Tala Tayoun ◽  
Marianna Garonzi ◽  
Genny Buson ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Epithelial To Mesenchymal Transition ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Anaplastic Lymphoma

AbstractGatekeeper mutations are identified in only 50% of the cases at resistance to Anaplastic Lymphoma Kinase (ALK)-tyrosine kinase inhibitors (TKIs). Circulating tumor cells (CTCs) are relevant tools to identify additional resistance mechanisms and can be sequenced at the single-cell level. Here, we provide in-depth investigation of copy number alteration (CNA) heterogeneity in phenotypically characterized CTCs at resistance to ALK-TKIs in ALK-positive non-small cell lung cancer. Single CTC isolation and phenotyping were performed by DEPArray or fluorescence-activated cell sorting following enrichment and immunofluorescence staining (ALK/cytokeratins/CD45/Hoechst). CNA heterogeneity was evaluated in six ALK-rearranged patients harboring ≥ 10 CTCs/20 mL blood at resistance to 1st and 3rd ALK-TKIs and one presented gatekeeper mutations. Out of 82 CTCs isolated by FACS, 30 (37%) were ALK+/cytokeratins-, 46 (56%) ALK-/cytokeratins+ and 4 (5%) ALK+/cytokeratins+. Sequencing of 43 CTCs showed highly altered CNA profiles and high levels of chromosomal instability (CIN). Half of CTCs displayed a ploidy >2n and 32% experienced whole-genome doubling. Hierarchical clustering showed significant intra-patient and wide inter-patient CTC diversity. Classification of 121 oncogenic drivers revealed the predominant activation of cell cycle and DNA repair pathways and of RTK/RAS and PI3K to a lower frequency. CTCs showed wide CNA heterogeneity and elevated CIN at resistance to ALK-TKIs. The emergence of epithelial ALK-negative CTCs may drive resistance through activation of bypass signaling pathways, while ALK-rearranged CTCs showed epithelial-to-mesenchymal transition characteristics potentially contributing to ALK-TKI resistance. Comprehensive analysis of CTCs could be of great help to clinicians for precision medicine and resistance to ALK-targeted therapies.

scholarly journals Real-world osimertinib for EGFR mutation-positive non-small-cell lung cancer with acquired T790M mutation

2020 ◽  
Vol 16 (21) ◽  
pp. 1537-1547
Author(s):  
Fumio Imamura ◽  
Madoka Kimura ◽  
Yukihiro Yano ◽  
Masahide Mori ◽  
Hidekazu Suzuki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Clinical Trial Registration

Aim: Osimertinib is a key drug for EGFR mutation-positive non-small-cell lung cancer (NSCLC). As the hazards ratio of overall survival in comparison with first-generation EGFR-tyrosine kinase inhibitors was almost similar between FLAURA and ARCHER 1050, salvage use of osimertinib is still a treatment option. Patients & methods: We retrospectively analyzed the clinical courses of EGFR mutation-positive NSCLC patients who were potential candidates for salvage osimertinib. Results: Among 524 patients enrolled from five hospitals, 302 patients underwent biopsy, with 52.6% detection rate of T790M. Osimertinib was administered in 93.6% of the T790M-positive patients. The overall response rate and median progression-free survival time of osimertinib were calculated with 147 patients, to be 55.6% and 17.2 months, respectively. Conclusion: Osimertinib is active for T790M-driven acquired resistance in EGFR-mutant NSCLC, but the detection of T790M was unsatisfactory. Clinical Trial Registration: UMIN000028989 (UMIN Clinical Trials Registry)

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