Ignite Creation Date:
2024-05-05 @ 10:26 PM
Last Modification Date:
2024-10-26 @ 10:18 AM
Study NCT ID:
NCT01100840
Status:
UNKNOWN
Last Update Posted:
2013-12-11
First Post:
2009-09-14
Brief Title:
A Retrospective Study of Biomarkers in Non-Small Cell Lung Cancer
Sponsor:
National University Hospital Singapore
Organization:
National University Hospital Singapore
Study Overview
Official Title:
A Retrospective Study of Biomarkers in Non-small Cell Lung Cancer
Status:
UNKNOWN
Status Verified Date:
2013-12
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is
1 To characterize the types and frequency of molecular alterations to the epidermal growth factor receptor EGFR pathway FGFR4 and EML-ALK in Asian patients with non-small cell lung cancer
2 To identify candidate biomarkers of importance in the EGFR and estrogen pathways
Most if not all human malignancies including lung cancer are caused by somatic alterations of the genome leading to activation of oncogenes or inactivation of tumor suppressor genes and their resultant oncogenic effects In addition to mutations increased chromosomal copy number by amplification or polysomy and DNA methylation are other mechanisms of oncogene activation and tumour suppressor gene inactivation respectively
Little is known about the relationship between these oncogenes of the EGFR family and the recently described oncogenes FGFR4 and fusion gene EML4-ALK Recent data suggests molecularly defined subgroups of non-small cell lung cancer NSCLC exist and can be used to predict for sensitivity to targeted agents erlotinib or gefitinib or cytotoxic chemotherapy pemetrexate gemcitabine platinum agents The findings that estrogen receptors are present in lung tumours and that estrogen can stimulate growth and proliferation of lung cancers in vitro and in vivo are provocative Further studies to evaluate the role of estrogens and other sex hormones in lung cancer are warranted
A further understanding of the molecular indicators of lung cancer prognosis and treatment prediction would improve drug development and patient treatment selection
Archived paraffin-embedded and fresh frozen NSCLC tumor tissue will be obtained via the Department of Pathology and the National University Tissue Repository respectively Clinico-pathological characteristics will be obtained from the case records Pathology and Tissue Repository DNA will be isolated using standard techniques Sequencing of genes in the EGFR signaling pathway EGFR KRAS ErbB2 ErbB3 MET PI3K and BRAF as well as FGFR4 Unstained slides from the paraffin-embedded tissue will be obtained and subjected to fluoresce in vitro hybridization FISH for breakpoints in the EML4 and ALK genes as previously described For cases that have been snap-frozen RNA will be extracted and EML4-ALK fusions will be confirmed using RT-PCR and pre-specified primers To analyse the expression of proteins of putative relevance to EGFR function such as EGFR ErbB2 ErbB3 AKT MET STAT ERK MAPK cyclin D1 CEBPa downstream effects of EGFR cell proliferation Ki-67 angiogenesis CD34 VEGF-A apoptosis bcl-2 metastasis and hormonal influence oestrogen and progesterone receptors aromatase TMA technology will be utilised The status of the tumor suppressor genes PTEN and CEBPa will be analysed
1 To characterize the types and frequency of molecular alterations to the epidermal growth factor receptor EGFR pathway FGFR4 and EML-ALK in Asian patients with non-small cell lung cancer
2 To identify candidate biomarkers of importance in the EGFR and estrogen pathways
Most if not all human malignancies including lung cancer are caused by somatic alterations of the genome leading to activation of oncogenes or inactivation of tumor suppressor genes and their resultant oncogenic effects In addition to mutations increased chromosomal copy number by amplification or polysomy and DNA methylation are other mechanisms of oncogene activation and tumour suppressor gene inactivation respectively
Little is known about the relationship between these oncogenes of the EGFR family and the recently described oncogenes FGFR4 and fusion gene EML4-ALK Recent data suggests molecularly defined subgroups of non-small cell lung cancer NSCLC exist and can be used to predict for sensitivity to targeted agents erlotinib or gefitinib or cytotoxic chemotherapy pemetrexate gemcitabine platinum agents The findings that estrogen receptors are present in lung tumours and that estrogen can stimulate growth and proliferation of lung cancers in vitro and in vivo are provocative Further studies to evaluate the role of estrogens and other sex hormones in lung cancer are warranted
A further understanding of the molecular indicators of lung cancer prognosis and treatment prediction would improve drug development and patient treatment selection
Archived paraffin-embedded and fresh frozen NSCLC tumor tissue will be obtained via the Department of Pathology and the National University Tissue Repository respectively Clinico-pathological characteristics will be obtained from the case records Pathology and Tissue Repository DNA will be isolated using standard techniques Sequencing of genes in the EGFR signaling pathway EGFR KRAS ErbB2 ErbB3 MET PI3K and BRAF as well as FGFR4 Unstained slides from the paraffin-embedded tissue will be obtained and subjected to fluoresce in vitro hybridization FISH for breakpoints in the EML4 and ALK genes as previously described For cases that have been snap-frozen RNA will be extracted and EML4-ALK fusions will be confirmed using RT-PCR and pre-specified primers To analyse the expression of proteins of putative relevance to EGFR function such as EGFR ErbB2 ErbB3 AKT MET STAT ERK MAPK cyclin D1 CEBPa downstream effects of EGFR cell proliferation Ki-67 angiogenesis CD34 VEGF-A apoptosis bcl-2 metastasis and hormonal influence oestrogen and progesterone receptors aromatase TMA technology will be utilised The status of the tumor suppressor genes PTEN and CEBPa will be analysed
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None