Ignite Creation Date:
2024-05-06 @ 12:30 AM
Last Modification Date:
2024-10-26 @ 10:51 AM
Study NCT ID:
NCT01596374
Status:
UNKNOWN
Last Update Posted:
2013-12-11
First Post:
2012-04-02
Brief Title:
Clinical Relevance of ROS V-ros UR2 Sarcoma Virus Oncogene Homolog Aberrations in Solid Tumours
Sponsor:
National University Hospital Singapore
Organization:
National University Hospital Singapore
Study Overview
Official Title:
None
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:
Alterations involving the ROS v-ros UR2 sarcoma virus oncogene homolog 1 gene such as mutations overexpression and gene rearrangements has been implicated in carcinogenesis and has been demonstrated to be a relevant target for ALK inhibitors While emerging reports have demonstrated the role of ROS rearrangement in non-small cell lung cancer and cholangiocarcinoma the functional significance of ROS dysregulation in solid tumors remain largely unstudied The investigators aims are 1 To characterize the frequency of ROS gene fusion ROS protein overexpression and ROS gene mutations in cell lines and tumors from patients with hepatocellular carcinoma colorectal gastric breast ovarian cholangiocarcinoma and non-small cell lung cancer 2 To identify novel ROS gene variants in human solid tumors harboring ROS aberrations using next generation sequencing NGS 3 To determine the functional relevance of novel ROS gene variants identified with NGS 4 To characterize the sensitivity of cells with functionally relevant ROS aberrations using ROS tyrosine kinase inhibitors ROS fusions and protein overexpression will be screened in a panel of cell lines and primary tumors using Fluorescence In-situ Hybridization and immunohistochemistry respectively Targeted next-generation sequencing will be applied to identify ROS variants in matching cancer types demonstrating high levels of gene fusion and protein overexpression Functional characterization of novel ROS variants will be performed by silencing shRNA and overexpressing candidate cell lines with the respective ROS mutationsfusions and evaluating their effects on biological functions including cell proliferation migration invasion and apoptosis as well as sensitivity against ROSALK inhibitors The investigators anticipate findings from this study will improve the investigators understanding of aberrant ROS signaling in an expanded group of cancer types and potentially identifying a larger group of cancer patients that will benefit from ROS targeted therapy
Further insight of the role of ROS receptor tyrosine kinase will confirm it as a therapeutic target in human solid tumors and hence expand the indication of crizotinib and other dual ALK ROS inhibitors Furthermore given the rarity of ROS fusion receptor tyrosine kinase in reported cancers defining the epidemiology of ROS aberrations in other unreported cancers harboring ROS pathway activation is essential to properly design future clinical trials of ROS inhibitors The validation of ROS receptor tyrosine kinase will also provide a new therapeutic target in the treatment of cancer and expand the role of novel targeted agents Findings from this study will further the investigators knowledge on the oncogenic functions of the ROS and the application of ROS inhibitors in an extended group of solid tumors
Further insight of the role of ROS receptor tyrosine kinase will confirm it as a therapeutic target in human solid tumors and hence expand the indication of crizotinib and other dual ALK ROS inhibitors Furthermore given the rarity of ROS fusion receptor tyrosine kinase in reported cancers defining the epidemiology of ROS aberrations in other unreported cancers harboring ROS pathway activation is essential to properly design future clinical trials of ROS inhibitors The validation of ROS receptor tyrosine kinase will also provide a new therapeutic target in the treatment of cancer and expand the role of novel targeted agents Findings from this study will further the investigators knowledge on the oncogenic functions of the ROS and the application of ROS inhibitors in an extended group of solid tumors
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