Active clinical trials for "Lung Neoplasms"

Lung cancer is the leading cause of cancer deaths in Taiwan. The carcinogen in the environment is a key role in the development of lung cancer, and one of its main resource is tobacco. Activated carcinogens in the organism lead to mutations of crucial oncogenes resulting in tumor development. Genes such as Cytochrome P-450 family, GST (glutathione S-transferase) family, UGT (UDP-Glucuronosyltransferase) family, ERCC-1(excision repair cross-complementing rodent repair deficiency),ERCC-4 and ERCC-5,are encoding antioxidant enzymes or involving in the DNA repair process and the production of some transcription factors. In recent years, many studies have shown the correlation between these genes and the susceptibility of lung cancer. Each gene has a different role in the tumor development pathway. CYP, UGT, GST, NAT2 (N-acetyltransferase 2) and NQO1(NAD(P)H:quinono oxidoreductase 1) involve in the production of antioxidant enzymes. The antioxidant enzymes can detoxificate hydrogen peroxide or defense against oxidative stress. However, the genetic polymorphisms may influence the function of detoxification, which cause the increase in the susceptibility of lung cancer. P53 and MDM2 genes play important roles in the production of tumor-suppression proteins and the regulation of transcription factors, which may regulate the growth and the apoptosis of cell cycle and influence the susceptibility of lug cancer. The polymorphisms in ERCC genes may cause the damage in the DNA repair process which might also cause increase in lung cancer susceptibility. The overexpression of epidermal growth factor receptor is highly correlated with increasing risk of the non-small cell lung cancers. The overexpression may induce the proliferation of cancer cells and the inhibition of the apatosis. Therefore, in recent years, EGFR has been widely studied as the new target of the drugs and the susceptibility of the lung cancer. In addition,the genetic polymorphisms in drug metabolism channel proteins, like OCT2 (organic cation transporter), ATP7A, ATP7B and ABC (ATP-binding cassette) transporter may have influence on the metabolism, the efficacy and the toxicity of the drugs.

Lung cancer is the leading cause of cancer death in Hong Kong. Lung adenocarcinomas is the most common type, accounting for 70% of lung cancer and the molecular target of epidermal growth factor receptor (EGFR) gene mutation at exons 18 - 21 is present in about 50% of lung adenocarcinomas. The v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-ras) mutations are commonly present in the other 50% that are EGFR wildtype. EGFR and K-ras mutations are found to be mutually exclusive in the same tumor. EGFR-tyrosine kinase inhibitor (TKI) can be used as treatment for EGFR mutated tumors while no specific targeted therapy can be recommended for EGFR wildtype tumors and these patients often receive chemoirradiation, which is toxic and clinical response is suboptimal. There is a need to find alternative molecular pathways/targets in EGFR wildtype lung adenocarcinomas. Even with EGFR mutations, good clinical response to EGFR-TKI is achieved in about 70% of these patients. This would mean suboptimal targeting of the EGFR gene or the presence of alternative pathways mediating tumor progression and susceptibility to therapy. Exploration of molecular pathways in lung cancer may allow for discovery of new molecular targets for therapeutic development. Neutrophil infiltration is frequently observed in lung cancer. Recognized similarities between neutrophils and cancer cells include (i) ability to circulate as single cells; (ii) target attachment via vascular system; (iii) target invasion. The major difference is that migrated neutrophils will undergo apoptosis while cancer cells can escape apoptosis. This led to the postulation that neutrophils and cancer cells may share similar inflammatory cascades by secreting a similar panel of proteases, and one of these could be neutrophil elastase (NE). Animal studies demonstrated that NE from neutrophils moves into lung tumor cells and mediates lung tumor growth via degradation of Insulin receptor substrate-1 (IRS-1), leading to activation of intracellular phosphoinositide-3-kinase (PI3k) and the v-akt murine thymoma viral oncogene homolog 1 (Akt) signaling pathways and the intracellular tyrosine kinase of the platelet-derived growth factor receptor (PDGFR). The aims of this study are to demonstrate NE activities and the subsequent signaling cascades activated in lung cancer cells, and to verify NE and its related pathway activation in clinical lung cancer specimen. This study will conclude the roles of NE and the therapeutic potential of NE/IRS-1/PI3K/PDGFR pathways in EGFR wildtype lung adenocarinomas.

This is an exploratory study in patients with locally advanced or metastatic Non-small cell lung cancer. Patients who are eligible to apply for Extended Access Program of crizotinib must have ALK translocation detected by RT-PCR, IHC or FISH analyses methods.

Environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs) were reviewed as the major risk factors for lung cancer development. In this proposal, the investigators collected fifteen kinds of major PAHs and the investigators would like to perform the following studies: Study the gene expression and subcellular localization of GNMT in the normal-tumor tissue pairs of lung cancer patients. Study the associations of the polymorphisms of GNMT in lung cancer patients and the susceptibility to lung cancer; To assess the allelic loss at GNMT and determined the LOH rate of GNMT in the normal-tumor tissue pairs of lung cancer patients. Study the associations of the copy number variation (CNV) of GNMT and the susceptibility to lung cancer; Study the interaction between GNMT and polycyclic aromatic hydrocarbons (PAHs) in lung cancer cell lines.

The overall goal of this research is to enhance the investigators understanding of the pathways involved in lung cancer, and to identify new biomarkers and/or therapeutic targets. By comparing gene expression between normal lung tissue and tumors growing in lung-specific C/EBPa KO mice, the investigators have identified the Bmi-1 proto-oncogene as being abnormally upregulated in C/EBPa-deleted tumors. Subsequently, the investigators have validated this observation in human lung cancer, implicating the investigators KO mice are an effective discovery tool for lung cancer research. Through similar approaches, the investigators have already identified (Sonic Hedgehog, SHH), and plan to identify other pathways which are abnormally regulated in C/EBPa-/- tumors. In parallel, the investigators will proceed to define the clinical relevance of the SHH pathway and the other newly-discovered molecular aberrations, by analyzing their expression and correlate it to C/EBPa expression on the samples of patients with NSCLC at NUHS. If the investigators preliminary data on Bmi-1 will be confirmed, this proto-oncogene may generate useful correlates that could be used in diagnosis and treatment of lung cancer, as well as identify new prognostic/predictive markers in lung cancer. Similarly, SHH pathway-components may behave as potential biomarkers and therapeutic tools for C/EBPa-related lung cancers. This proposal seeks to test the hypothesis that pathways which are dysregulated in lung tumors growing in a lung-specific C/EBPa KO model can be utilized as discovery tools to identify genes involved in human lung cancer pathogenesis.

Lung cancer remains the most common cause of cancer-related death in the world. The major advances in treatment of lung cancer have brought only minor improvements in survival therefore novel systemic treatment methods are urgently needed. Protein levels are regulated by the protein homeostasis network that generates and protects the protein fold (ER and Golgi included). The heat shock protein 90 (Hsp90) is an essential molecular chaperon involved in the posttranslational folding and stability of proteins. Hsp90 inhibition leads to accumulation of unfolded proteins and ER stress. The therapeutic efficacy of such inhibition may be augmented by co-administering it with other drugs that disrupt ER-Golgi homeostasis like histone deacetylase (HDAC) or proteasome inhibitors. ER-Golgi homeostasis disruption affects a wide network of proteins and pathways as such affords a systemic target. Thus, the investigators aimed to examine the effect of combined treatment of Hsp90 antagonist with proteasome or HDAC inhibitors on human lung cancer cell lines and primary cells.

RATIONALE: Collecting and storing samples of sputum and tissue to study in the laboratory may help doctors identify biomarkers related to cancer. PURPOSE: This research study is looking samples of sputum and tissue from lung cancer patients, participants at high risk for developing lung cancer, and from healthy volunteers (both smokers and non-smokers).

Evaluation of the frequency and clinical characteristics of ALK rearrangements in Latin-American countries. Latin American countries are heterogeneous in terms of lung cancer incidence, ethnicity, and exposure to potential carcinogens. The discovery of the echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) translocation as an oncogenic driver has led to the development of novel therapies with activity in vitro and in the clinic.

The purpose of this study is to evaluate the use of Dynamic PET/CT as a tool to assess disease response to anti-cancer therapy in Lung Cancer patients.

The purpose of this study is to investigate the changes of lymphocyte subsets in chemotherapy course of patients with non-small cell lung cancer