Breast Cancer Subtype Characterization Through Patient's Derived Organoids". (BCinsightPDO)
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Breast Cancer
- Sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Enrollment
- 306
- Locations
- 1
- Primary Endpoint
- evaluate the sensitivity of ER/PR+, HER2+ and TNBC PDO to novel therapeutic agents in clinical trials for BC or other cancer types
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
Development of tools to predict patients chemo-sensitivity and identification of corresponding biomarkers is an urgent challenge for BC patients lacking targeted therapies, such as TNBC, or for patients experiencing relapse after adjuvant chemotherapy or targeted therapies.
The refinement of 3D-cultivation techniques, experienced in the last decade, has allowed cultivation of patients-derived cancer cells in organotypic structures, named patient-derived organoids (PDO), which preserve histologic, genomic and transcriptomic features of primary tumors. PDO allow propagation, pharmacological treatment and genetic manipulation of patients-derived cancer cells in a close to physiology setting, thus representing a promising tool in the development of personalized therapies
Detailed Description
PDO have been shown to efficiently recapitulate ex-vivo the in vivo response to hormonal treatment of BC patients. These observations point to PDO as potential valuable tools for a rapid, personalized prospective evaluation of patient-specific chemo-sensitivity. Moreover, PDO can represent a valuable ex-vivo platform for screening new treatments, or combination of current treatments, in a medium-to-high-throughput fashion. Thus, development of a stable collection of PDO representing the heterogeneity of BC subtypes, including the evolution of recurrent disease, represents an extremely useful resource for both prospective and retrospective studies aimed at understanding the molecular phenotype associated with chemoresistance.
Investigators
Eligibility Criteria
Inclusion Criteria
- •women diagnosed with primary BC, eligible for surgical resection of the tumor according to national and international guidelines.
- •age between 18 and 70 years; newly diagnosed breast neoplasms, tumor size of at least 1.5 cm diameter.
Exclusion Criteria
- •breast cancer diagnosed during pregnancy, neoadiuvant chemotherapy
Outcomes
Primary Outcomes
evaluate the sensitivity of ER/PR+, HER2+ and TNBC PDO to novel therapeutic agents in clinical trials for BC or other cancer types
Time Frame: 42 months
PDO will be tested for their susceptibility to the therapeutic agents administered to the corresponding patients and/or to novel therapeutic agents in clinical trials for BC or other cancer types by performing cell viability assays and clonogenic potential assay before and after treatments. Sensitivity to the tested drugs will be evaluated on the basis of the known maximal plasma concentration of the drug (Cmax): sensitive if survival is \<50% at Cmax dose; resistant if survival is \>50% at Cmax dose. Dichotomic variable: Yes (sensitive)/No (resistant)
evaluate the histological and molecular conformity (yes/no) between PDO and matched primary and/or recurrent BC sample, in order to develop a live biobank of ER/PR+, HER2+ and TNBC PDO.
Time Frame: 36 months
Part of each surgical specimen will be used to obtain PDOs according to established procedures, part will be fixed and paraffin embedded for histological analysis and part will be flash-frozen for DNA, RNA and protein analyses. At first passages, organoids will be characterized for histologic and cytologic features. PDOs that faithfully recapitulate features of the matched primary tumor will be analysed for genomic features and splicing-sensitive transcriptomic signatures by next generation sequencing (NGS). Dichotomic variable: Yes (conform)/No (not conform)
Secondary Outcomes
- test the synergizing effects of agents splicing-targeting treatments to immunotherapies by co-culture experiments with autologous immune cells(42 months)
- test the sensitivity of PDO to splicing-targeting treatments, either alone or in combination with other therapies(42 months)