Clinical trial NCT03467308: Signaling Pathways Targeting Colorectal Cancer in Egypt
Official title: Identification of New Signaling Pathways Targeting Colorectal Cancer in Egyptian Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Cancer
Keywords: colorectal cancer
TIGAR
TRIM59
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2018-03-16
Enrollment: 180
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: * All Patients confirmed histopathologically to have early stages of colorectal cancer admitted to General Surgery Department -Assiut University Hospital for CRC resection.
* Risky group patients (including those with ulcerative colitis, chron's disease, familial adenomatous polyposis) undergoing diagnostic colonoscopy.

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 4.2% 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-2,6-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 PI3K/AKT 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.

Eligibility criteria: Inclusion Criteria:

* All Patients confirmed histopathologically to have early stages of colorectal cancer.
* Risky group patients (including those with ulcerative colitis, chron's disease, familial adenomatous polyposis).

Exclusion Criteria:

* Patients with previous history of CRC treated with chemotherapy or presence of other types of cancer.

Primary outcomes:
measure: Measure TIGAR in the study groups.
timeFrame: 1 YEAR
measure: Measure TRIM59 in the study groups.
timeFrame: 1Year
Secondary outcomes:
measure: Targeting new prognostic and therapeutic markers for colorectal cancer.
timeFrame: 1 year
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Assiut University- faculty of medicine -Medical biochemistry department
Study officials:
affiliation: Assiut University
name: Asmaa Alaaeldeen Kamal, MD (PhD student)
role: PRINCIPAL_INVESTIGATOR
affiliation: Assiut University
name: Ragaa Hamdy Salama, Professor (MD)
role: STUDY_DIRECTOR
affiliation: Assiut University
name: Maha Ali Essam al-Din, lecturer (MD)
role: STUDY_DIRECTOR
affiliation: Assiut University
name: Marwa AbdelHafiz Abdel Hassan, lecturer (MD)
role: STUDY_DIRECTOR
affiliation: Assiut University
name: Ahmed Ali Abdel Motelb, lecturer (MD)
role: STUDY_DIRECTOR
References:
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