SMYD3-Driven Metabolic Rewiring in Colorectal Liver Metastases

NCT07497789 | Not Yet Recruiting

• 1 other identifier: AIRC_ IG 34634
• Study Type: observational
• Target: 156
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study focuses on patients with colorectal cancer undergoing surgery for the primary tumor and/or liver metastases. Tumor samples collected during surgery will be used to generate patient-derived models (primary cultures, spheroids, and organoids) to study colorectal cancer stem cells. The main objective is to investigate the role of the lysine methyltransferase SMYD3 in metabolic reprogramming and adaptation to oxidative stress that enable colorectal cancer cells to survive and grow in the liver. Previous work has shown that SMYD3 is overexpressed in colorectal cancer, promotes drug resistance, and regulates key oncogenic pathways, including c-MYC and the AMPK/mTOR axis. By identifying SMYD3-dependent pathways and pharmacologic vulnerabilities in cancer stem cells within liver metastases, this study aims to support the development of new therapeutic strategies that combine SMYD3 inhibitors with approved or experimental agents targeting tumor metabolism and oxidative stress responses

Conditions

Liver Metastases From Colorectal Primary Cancer; CRC (Colorectal Cancer)

Keywords

Colorectal cancer; liver metastases; liver metastases from colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Molecular and Cellular mechanisms

  Identification of the molecular and cellular mechanisms involved in metastatic progression that depend on the methyltransferase SMYD3

  At the time of the surgery

Study Arms (3)

Patients with CRC (colorectal cancer)

Patients undergoing surgery for primary colorectal carcinoma, without liver metastases

Patients with colorectal cancer (CRC) and liver metastase

Patients undergoing surgery for primary colorectal carcinoma who simultaneously present liver metastases from colorectal carcinoma. In this case, tissue samples will be taken from both the colorectal carcinoma and the liver metastases

Patients with liver metastase

Patients undergoing surgery for the resection of liver metastases from previously operated colorectal cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study is a multicenter prospective observational study and involves the collection of biological samples from patients undergoing surgery for CRC and/or liver metastases

You may qualify if:

• Common criteria
• Age ≥ 18 years.
• Availability of residual tumor tissue from the surgical procedure that is not required for diagnostic purposes.
• Signed written informed consent for the use of biological samples for research purposes.
• Cohort/Arm 1 (Colon-rectal tumor resection)
• \- Patients undergoing surgical resection of colorectal cancer.
• Cohort/Arm 2 (Primary tumor and liver metastases resection) - Patients undergoing surgical resection of the primary colorectal tumor and liver metastases from colorectal carcinoma.
• Cohort/Arm 3 (Liver metastases resection only)
• \- Patients undergoing surgical resection of liver metastases from colorectal carcinoma previously resected at the primary site.

You may not qualify if:

• Age \< 18 years.
• Lack of signed informed consent

Sponsors & Collaborators

• University of Bari: collaborator
• Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis: lead

Biospecimen

Retention: SAMPLES WITH DNA

During the surgical procedure, tumor tissue samples and, when available, adjacent non-neoplastic tissue will be collected exclusively from residual material from the surgical procedure that is not required for histopathological diagnosis. Colorectal cancer (CRC) tissue and tissue from liver metastases of CRC will be collected.

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Cristiano Simone, MD

CONTACT

+390804994615; cristiano.simone@irccsdebellis.it

Martina Lepore Signorile, Biologist

CONTACT

+390804994615; martina.lepore@irccsdebellis.it

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 23, 2026
• First Posted: March 27, 2026
• Study Start: May 10, 2026
• Primary Completion (Estimated): May 10, 2027
• Study Completion (Estimated): May 10, 2028
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share