scholarly journals Receptor Tyrosine Kinases and Inhibitors in Lung Cancer

2004 ◽  
Vol 4 ◽  
pp. 589-604 ◽  
Author(s):  
Evan Pisick ◽  
Simha Jagadeesh ◽  
Ravi Salgia
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Vegf Receptor ◽  
Lung Cancers

Lung cancer is a deadly disease with high mortality and morbidity. Most cases of lung cancer are due to non-small cell carcinoma, with 16% of cases being small cell carcinoma. The biology at a cellular level is of interest at many levels. Knowing cellular pathways helps to further enhance our knowledge of how lung cancer cells survive, proliferate, and metastasize. The receptor tyrosine kinases (RTKs) located at the cellular membrane are becoming of great interest as sites for targeted therapies for lung cancers. This review will discuss the RTKs that are involved in lung cancers and the newer therapies that are being tested. We will specifically discuss receptors such as epidermal growth factor receptor, c-Kit receptor, VEGF receptor, c-Met receptor, insulin growth factor receptor, and Eph receptor. The inhibitors against the specific RTKs are in various preclinical and clinical trials, and this will be detailed.

Sunitinib: From Rational Design to Clinical Efficacy

2007 ◽  
Vol 25 (7) ◽  
pp. 884-896 ◽  
Author(s):  
Laura Q.M. Chow ◽  
S. Gail Eckhardt
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Antitumor Activity ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Small Cell Lung

Sunitinib (SU011248) is an oral small molecular tyrosine kinase inhibitor that exhibits potent antiangiogenic and antitumor activity. Tyrosine kinase inhibitors such as SU6668 and SU5416 (semaxanib) demonstrated poor pharmacologic properties and limited efficacy; therefore, sunitinib was rationally designed and chosen for its high bioavailability and its nanomolar-range potency against the antiangiogenic receptor tyrosine kinases (RTKs)—vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR). Sunitinib inhibits other tyrosine kinases including, KIT, FLT3, colony-stimulating factor 1 (CSF-1), and RET, which are involved in a number of malignancies including small-cell lung cancer, GI stromal tumors (GISTs), breast cancer, acute myelogenous leukemia, multiple endocrine neoplasia types 2A and 2B, and familial medullary thyroid carcinoma. Sunitinib demonstrated robust antitumor activity in preclinical studies resulting not only in tumor growth inhibition, but tumor regression in models of colon cancer, non–small-cell lung cancer, melanoma, renal carcinoma, and squamous cell carcinoma, which were associated with inhibition of VEGFR and PDGFR phosphorylation. Clinical activity was demonstrated in neuroendocrine, colon, and breast cancers in phase II studies, whereas definitive efficacy has been demonstrated in advanced renal cell carcinoma and in imatinib-refractory GISTs, leading to US Food and Drug Administration approval of sunitinib for treatment of these two diseases. Studies investigating sunitinib alone in various tumor types and in combination with chemotherapy are ongoing. The clinical benchmarking of this small-molecule inhibitor of members of the split-kinase domain family of RTKs will lead to additional insights regarding the biology, potential biomarkers, and clinical utility of agents that target multiple signaling pathways in tumor, stromal, and endothelial compartments.

KIT and platelet-derived growth factor receptor α gene expression in laryngeal small cell carcinoma

2010 ◽  
Vol 124 (12) ◽  
pp. 1340-1343 ◽  
Author(s):  
T Kanazawa ◽  
M Nokubi ◽  
K Takizawa ◽  
S Matsuzawa ◽  
A Shinnabe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Case Reports ◽  
Direct Sequencing ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Platelet Derived Growth Factor ◽  
Tumour Metastasis

AbstractObjective:Small cell carcinoma has the worst prognosis of all laryngeal neoplasms. In order to further characterise this tumour, with a view to development of new therapeutic approaches, we report the results of KIT gene and platelet-derived growth factor receptor α gene expression analysis, for two extremely rare cases of primary small cell carcinoma of the larynx.Method:Case reports, including immunohistochemical study, and review of the literature.Results:We present two patients with laryngeal small cell carcinoma, who died from tumour metastasis to the lungs and brain despite aggressive treatment. Immunohistochemical studies revealed positive reactions for KIT gene expression and platelet-derived growth factor α gene expression in patient one, and for KIT gene expression in patient two. Molecular genetic analysis, using polymerase chain reaction direct sequencing, identified no mutations of the KIT or platelet-derived growth factor receptor α genes.Conclusion:Although further investigation is necessary regarding KIT gene expression and platelet-derived growth factor receptor α gene expression in laryngeal small cell carcinoma, the reported results suggest that these genes may be significant in the development of molecular targeted therapy.

MicroRNA-200a Targets EGFR and c-Met to Inhibit Migration, Invasion, and Gefitinib Resistance in Non-Small Cell Lung Cancer

2015 ◽  
Vol 146 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Qiang Zhen ◽  
Junfeng Liu ◽  
Lina Gao ◽  
Jiabao Liu ◽  
Renfeng Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tyrosine Kinases ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

Lung cancer, especially non-small cell lung cancer (NSCLC), is the major cause of cancer death worldwide. Mutations in epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-Met), both of which are receptor tyrosine kinases, have been identified in a considerable percentage of NSCLC patients. EGFR and c-Met share the same downstream pathways and cooperate not only in promoting metastasis but also in conferring resistance to tyrosine kinase inhibitor (TKI) therapies in NSCLC. MicroRNAs (miRNAs) are a family of small non-coding RNAs, usually 21-25 nucleotides long, and are critical in regulating gene expression. Abnormal miRNA expression has been implicated in the initiation and progression in many forms of cancers, including lung cancer. In this study, we found that miR-200a is downregulated in NSCLC cells, where it directly targets the 3′-UTR of both EGFR and c-Met mRNA. Overexpression of miR-200a in NSCLC cells significantly downregulates both EGFR and c-Met levels and severely inhibits cell migration and invasion. Moreover, in NSCLC cell lines that are resistant to gefitinib, a drug often used in TKI therapies to treat NSCLC, miR-200a expression is able to render the cells much more sensitive to the drug treatment.

scholarly journals Histological Transformation to Small Cell Carcinoma of an Adenosquamous Carcinoma of the Lung With Epidermal Growth Factor Receptor Mutation in Exons 20 and 21 After Treatment With Erlotinib: Case Report

2019 ◽  
Vol 13 ◽  
pp. 117954841987299
Author(s):  
Liliana Fernández-Trujillo ◽  
Laura Tapia ◽  
Marcela Vallejo ◽  
Marisol Aguirre ◽  
Juliana Lores ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Adenosquamous Carcinoma ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Mechanisms Of Resistance ◽  
Epidermal Growth

Lung carcinoma currently represents 1 of the leading causes of death from cancer worldwide and regionally. The molecular identification of sensitive mutations of targeted treatment have changed the strategies of pharmacologic management in non-small cell lung carcinoma. However, mechanisms of resistance have been described, among them the change of histological type to small cell carcinoma. We present the case of a 46-year-old male patient, non-smoker, with a clinical history of a mass in the upper lobe of the right lung and an initial histological diagnosis of adenosquamous carcinoma of the lung, with the presence of mutations for epidermal growth factor receptor (EGFR) in exons 20 (S768I) and 21 (L858R). He received treatment with tyrosine kinase inhibitor (Erlotinib) with good clinical and radiological response. However, 1 year after the start of the medication, he consulted for a progressive onset of constitutional symptoms and respiratory symptoms, with radiographic worsening and new biopsy with a diagnosis of adenosquamous carcinoma with the adenocarcinoma component transformed to small cell carcinoma, with persistence of EGFR mutation. We describe the clinical, radiological, and laboratory characteristics as well as the outcome of this case. To conclude, among the mechanisms of resistance described to the treatment with tyrosine kinase inhibitors in patients with carcinomas with mutated EGFR, the transformation to small cell carcinoma besides being infrequent is particular, requiring a different diagnostic and therapeutic approach.

scholarly journals Activation of Stat3 by receptor tyrosine kinases and cytokines regulates survival in human non-small cell carcinoma cells

Oncogene ◽  
2003 ◽  
Vol 22 (27) ◽  
pp. 4150-4165 ◽  
Author(s):  
Lanxi Song ◽  
James Turkson ◽  
James G Karras ◽  
Richard Jove ◽  
Eric B Haura
Keyword(s):  
Cell Carcinoma ◽  
Small Cell Carcinoma ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Small Cell ◽  
Carcinoma Cells
Sign in / Sign up

Export Citation Format

Share Document