Ignite Creation Date:
2024-05-06 @ 11:14 AM
Last Modification Date:
2024-10-26 @ 12:42 PM
Study NCT ID:
NCT03467308
Status:
COMPLETED
Last Update Posted:
2020-05-11
First Post:
2018-02-20
Brief Title:
Signaling Pathways Targeting Colorectal Cancer in Egypt
Sponsor:
Assiut University
Organization:
Assiut University
Study Overview
Official Title:
Identification of New Signaling Pathways Targeting Colorectal Cancer in Egyptian Patients
Status:
COMPLETED
Status Verified Date:
2020-05
Last Known Status:
None
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:
Colorectal cancer CRC is the third most commonly diagnosed cancer and the second leading cause of cancer-related death worldwide In Egypt CRC constitutes 42 of all cancers with median age is 50 years old
Detailed Description:
The TP53-induced glycolysis and apoptosis regulator TIGAR is a transcriptional target of p53 TIGAR functions as a fructose-26-bisphosphatase decreasing the flux through the main glycolytic pathway Consequently glucose metabolism diverted into the pentose phosphate pathway PPP This results in TIGAR-mediated increase in cellular NADPH production which contributes to the scavenging of ROS by reduced glutathione and thus a lower sensitivity of cells to oxidative stress-associated apoptosis PPP also produce ribose phosphate for DNA synthesis and repair that play a role in tumor development and cell survival in tumor microenvironment A high expression level of TIGAR was observed in cancers such as breast cancer hepatocellular carcinoma intestinal cancer and glioblastoma These studies suggested that TIGAR may act as an oncogene that support cancer progression
The tripartite motif containing 59 TRIM proteins have been implicated in many biological processes including cell differentiation apoptosis transcriptional regulation and signaling pathways
It is related to several cancers The oncogenic effect of TRIM59 on tumor proliferation and migration has been studied in various cancers including gastric cancer osteosarcoma lung and CRC The biological activity of TRIM59 has been observed to be closely associated with the regulation of P53 TRIM59 interacts with P53 leading to P53 ubiquitination and degradation and consequently promotes tumor growth and migration TRIM59 functions as an oncogene in CRC progression It also activates the PI3KAKT pathway Increased activity of this pathway is often associated with tumor progression and resistance to cancer therapies AKT can control TIGAR protein translation by activation of mTOR
Targeting TRIM59 inhibition will inhibit PI3K-Akt pathway downregulate TIGAR protein translation This is in turn downregulates GSH levels increases ROS production leading to cell death and blocks the cellular proliferation and survival of cancer cells leading to tumor regression Therefore TRIM59 protein can serve as a new potential therapeutic target for CRC
The tripartite motif containing 59 TRIM proteins have been implicated in many biological processes including cell differentiation apoptosis transcriptional regulation and signaling pathways
It is related to several cancers The oncogenic effect of TRIM59 on tumor proliferation and migration has been studied in various cancers including gastric cancer osteosarcoma lung and CRC The biological activity of TRIM59 has been observed to be closely associated with the regulation of P53 TRIM59 interacts with P53 leading to P53 ubiquitination and degradation and consequently promotes tumor growth and migration TRIM59 functions as an oncogene in CRC progression It also activates the PI3KAKT pathway Increased activity of this pathway is often associated with tumor progression and resistance to cancer therapies AKT can control TIGAR protein translation by activation of mTOR
Targeting TRIM59 inhibition will inhibit PI3K-Akt pathway downregulate TIGAR protein translation This is in turn downregulates GSH levels increases ROS production leading to cell death and blocks the cellular proliferation and survival of cancer cells leading to tumor regression Therefore TRIM59 protein can serve as a new potential therapeutic target for CRC
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None