The Theranostic Value of STARD3 in Colorectal Cancer: The STAR Study

Study Overview
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Brief Summary
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This study aims at verifying the overexpression of STARD3 in both early and advanced CRC patients derived tissues, to identify the pathways underpinning tumorigenesis and cancer progression in which STARD3 is involved. Moreover its role as a dynamic biomarker of treatment response and its part in treatment sensitivity will be explored.

Detailed Description
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Colorectal cancer (CRC) is one of the most prevalent and deadly tumours in both men and women worldwide. An RNAi screening on 214 potential oncogenes described by the TCGA was performed and STARD3 was identified as potential theranostic target in mCRC. Considering the effects on cell viability and the druggability, STARD3 represents a strong candidate as a valid diagnostic and therapeutic target for mCRC patients. In recent years, organoids have become a research hotspot, showing a significant potential in the biological analysis of tumours. Patient derived organoids could be a viable platform to test clinically available drugs and/or promising new molecules to explore tumour sensitivity in an ex-vivo model. This is a longitudinal observational study on CRC patients derived tissues to verify the overexpression of STARD3 in both early and advanced CRC patients, to identify the pathways underpinning tumorigenesis and cancer progression in which STARD3 is involved through the development of cancer derived organoids, to explore its role as a dynamic biomarker of treatment response and to demonstrate its part in treatment sensitivity measured in tumour derived organoids compared to drug sensitivity observed in real-world patients.

Official Title
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The Theranostic Value of STARD3 in Colorectal Cancer: The STAR Study: a Monocentric Observational Study

Conditions
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Colorectal Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of colorectal cancer, independently from diagnosis stage. Age ≥18 years. Signed informed consent form. Availability of tissue and blood samples stored at the Institutional Biobank for research purposes. Exclusion Criteria: Patients for which the tumour biobanking process could compromise the diagnostic assessments. Pregnancy or breast-feeding. History of concomitant or previous malignancy in the previous 5 years, except for adequately treated cutaneous squamous cell carcinoma or surgically removed in situ cervical carcinoma.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of overexpression of STARD3 in both early and advanced CRC patients | Frequency of STARD3 overexpression in both early and advanced CRC patients | at enrolment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequencies of overexpression or downregulation of selected genes alteration related to STARD3 overexpression | Frequencies of overexpression or downregulation of selected genes alteration related to STARD3 overexpression. This analysis will be carried out in organoids cancer model | up to 5 years | 
| Presence of STARD3 overexpression as a prognostic factor | relation between presence of STARD3 overexpression (dichotomic variable) and disease-free survival (DFS) defined as time between enrollment and objective tumor progression using Kaplan Meyer method | from enrolment to at least 5 years | 
| Variation of STARD3 as a prognostic factor | STARD3 expression could change over the time and affect disease-free survival (DFS). Relation between variation of STARD3 overexpression (dichotomic variable) and DFS (defined as time between enrollment and objective tumor progression) will be accessed with Kaplan Meyer method. | from enrolment to at least 5 years | 
| Relation between presence of STARD3 overexpression and progression-free survival (PFS) | relation between presence of STARD3 overexpression (dichotomic variable) and progression-free survival (PFS) defined as time between enrollment and objective tumor progression or death whichever comes first, using Kaplan Meyer method | from enrolment to at least 5 years | 
| relation between variation of STARD3 overexpression and progression-free survival (PFS) | relation between variation of STARD3 overexpression (dichotomic variable) and progression-free survival (PFS) defined as time between enrollment and objective tumor progression or death whichever comes first, using Kaplan Meyer method | from enrolment to at least 5 years | 
| Relation between presence of STARD3 overexpression and Overall survival (OS | relation between presence of STARD3 overexpression (dichotomic variable) and Overall survival (OS) defined as time between enrollment and death, using Kaplan Meyer method | from enrolment to at least 5 years | 
| Relation between variation of STARD3 overexpression and Overall survival (OS) | Relation between variation of STARD3 overexpression (dichotomic variable) and Overall survival (OS) defined as time between enrollment and death, using Kaplan Meyer method | from enrolment to at least 5 years | 
| Difference in the mean variation of STARD3 level in patients receiving oncologic treatment, evaluated from start of treatment to the first revaluation and to disease progression | Difference in the mean variation of STARD3 level in patients receiving oncologic treatment, evaluated from start of treatment to the first revaluation and to disease progression | from enrolment to at least 5 years | 
| Demonstrate treatment sensitivity measured in tumour derived organoids | Description of IC50 value (inhibitory concentration 50) for each drug tested on tumour-derived organoids | up to 5 years | 
| Relation between treatment sensitivity measured in tumour derived organoids and treatment sensitivity in patients | Relation between IC50 (inhibitory concentration 50) calculated for each drug tested on patients' tumour-derived organoids and PFS of patients defined as time between enrollment and objective tumor progression or death whichever comes first. Relation will be measured with Hazard Ratio (HR) | up to 5 years | 
| Concordance between the presence of selected molecular alterations on primary tumour tissues and organoids | Concordance between the presence of selected molecular alterations on primary tumour tissues and organoids, frequencies will be reported and Cohen's Kappa will be calculated. | up to 5 years |