Ignite Creation Date:
2024-10-26 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 3:39 PM
Study NCT ID:
NCT06574373
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-26
Brief Title:
Identification of New Theranostic Biomarkers of Pancreatic Tumor Progression
Sponsor:
None
Organization:
None
Study Overview
Official Title:
New Theranostic Biomarkers of Intraductal Mucinous Neoplasm IPMN Progression to Pancreatic Cancer for Patients Outcome Improvement
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Intraductal papillary mucinous neoplasms IPMN are one of the main precursor lesions of pancreatic ductal adenocarcinoma PDAC a lethal disease predicted to become the second leading cause of cancer-related deaths in Western societies within a decade The mechanisms underlying IPMN progression are poorly understood The goal of IPMN management is to reduce the risk of patient death due to progression to PDAC through primary and secondary prevention namely early diagnosis and risk-reducing surgery High-risk IPMNs ie high-grade or main duct IPMNs which account for 57-90 of cases are referred for surgical resection while low-risk IPMNs 6-46 undergo periodic follow-up aimed at monitoring the acquisition of morphological features associated with malignancy over time However the clinical management of IPMN remains a significant challenge because the distinction between high and low-risk progression is based on imaging and histological criteria that are not unequivocally recognized and do not take into account the underlying biology of lesions that appear similar but are associated with different clinical behaviors Consequently patient risk stratification is often inaccurate leading to suboptimal treatment Approximately 1-11 of low-risk IPMN patients assigned to clinical follow-up have developed PDAC Therefore it is of paramount importance to improve the understanding of the biology and malignant potential of IPMN to improve prognosis and clinical management of affected patients and guide them toward personalized therapeutic approaches The availability of markers capable of stratifying IPMN based on their risk of progression to PDAC could enhance the current malignancy criteria assessed in clinical settings by more accurately identifying patients who strongly need surgical resection
2 - Study Objective The aim of this study is to identify and validate biomarkers capable of distinguishing between low-risk and high-risk IPMN progression to PDAC These biomarkers would help more accurately identify IPMN patients who could benefit from therapeutic intervention andor surgical resection in the future The study will include patients with IPMN followed at Fondazione Policlinico Gemelli IRCCS Fondazione G Pascale IRCCS Azienda Ospedaliera Universitaria Integrata Verona and Azienda Ospedaliera Universitaria Integrata di Messina
2 - Study Objective The aim of this study is to identify and validate biomarkers capable of distinguishing between low-risk and high-risk IPMN progression to PDAC These biomarkers would help more accurately identify IPMN patients who could benefit from therapeutic intervention andor surgical resection in the future The study will include patients with IPMN followed at Fondazione Policlinico Gemelli IRCCS Fondazione G Pascale IRCCS Azienda Ospedaliera Universitaria Integrata Verona and Azienda Ospedaliera Universitaria Integrata di Messina
Detailed Description:
To achieve our goal we have planned the following strategy
AIM1
The primary objective of the research is organized into a workflow of three experiments
1 Identification of genes and biological pathways associated with IPMN malignant transformation through transcriptomic and epigenetic characterization We aim to explore the molecular dynamics of tumor progression focusing on cellular heterogeneity and phenotypic transitions
2 Characterization of the microenvironment to understand its role in IPMN progression We will collect archival samples from 240 patients across four centers Sixty tissues will be selected based on cyst type and dysplasia grade We will use advanced technologies ATAC-seq ST to investigate cellular aspects of IPMN progression We will perform single-cell spatial transcriptomics and ATAC-seq on samples representing the entire evolution of pancreatic cancer RNA velocity and Pseudotime algorithms will be used to trace the evolution from normal duct cells to PDAC Spatial proteomics Akoya Phenoimager will be used to validate key IPMN markers
3 Identification and validation in plasma of selected patients using aptamer-based technology identifying differentially expressed markers in indolent IPMN invasive IPMN and PDAC Molecular analyses will be conducted at the coordinating center Fondazione Policlinico Gemelli plasma analyses at Dante Labs and validation at the coordinating center and the University of Verona
AIM2 observational
We will develop knowledge-based tools for diagnosing and treating IPMN and at-risk populations including
We will collect clinical data from 3600 patients and use machine learning to identify markers of malignancy improving IPMN management
AIM3 The coordinating and Verona centers will validate the role of key genes in IPMN carcinogenesis using CrisprCas9 in organotypic IPMN cultures Pharmacological or genetic targeting will validate genes modulated during carcinogenesis Candidates will be prioritized based on the literature and available drugs Identified molecules may serve as new biomarkers for IPMN progression improving prognosis and therapeutic strategies We will use models from precancerous lesions and pancreatic tumors to guide patients toward the most appropriate therapies
AIM1
The primary objective of the research is organized into a workflow of three experiments
1 Identification of genes and biological pathways associated with IPMN malignant transformation through transcriptomic and epigenetic characterization We aim to explore the molecular dynamics of tumor progression focusing on cellular heterogeneity and phenotypic transitions
2 Characterization of the microenvironment to understand its role in IPMN progression We will collect archival samples from 240 patients across four centers Sixty tissues will be selected based on cyst type and dysplasia grade We will use advanced technologies ATAC-seq ST to investigate cellular aspects of IPMN progression We will perform single-cell spatial transcriptomics and ATAC-seq on samples representing the entire evolution of pancreatic cancer RNA velocity and Pseudotime algorithms will be used to trace the evolution from normal duct cells to PDAC Spatial proteomics Akoya Phenoimager will be used to validate key IPMN markers
3 Identification and validation in plasma of selected patients using aptamer-based technology identifying differentially expressed markers in indolent IPMN invasive IPMN and PDAC Molecular analyses will be conducted at the coordinating center Fondazione Policlinico Gemelli plasma analyses at Dante Labs and validation at the coordinating center and the University of Verona
AIM2 observational
We will develop knowledge-based tools for diagnosing and treating IPMN and at-risk populations including
We will collect clinical data from 3600 patients and use machine learning to identify markers of malignancy improving IPMN management
AIM3 The coordinating and Verona centers will validate the role of key genes in IPMN carcinogenesis using CrisprCas9 in organotypic IPMN cultures Pharmacological or genetic targeting will validate genes modulated during carcinogenesis Candidates will be prioritized based on the literature and available drugs Identified molecules may serve as new biomarkers for IPMN progression improving prognosis and therapeutic strategies We will use models from precancerous lesions and pancreatic tumors to guide patients toward the most appropriate therapies
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