CDK4/6 Inhibitor (Palbociclib, Ribociclib, Abemaciclib): Evaluation of the response to CDK4/6 inhibitors (Palbociclib, Ribociclib, Abemaciclib) on selected Medulloblastoma (MB) patient-derived organoids (PDOs).
Study summary
Medulloblastoma (MB), a rare yet critical pediatric brain tumor, is divided into 4 molecular subgroups (WNT, SHH, Group 3, Group 4), each with distinct genetic profiles. Despite diagnostic and therapeutic advances, neurotoxicity from standard treatments (resection, radiotherapy, chemotherapy) and the need for long-term care remain challenges. CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib), approved for breast cancer, show potential in other tumors, but their efficacy in MB is unclear. Treatment resistance is a concern. This project aims to identify genetic markers of sensitivity to CDK4/6 inhibitors in MB, to improve therapies and overcome resistance.
Eligibility
Sex
ALL
Min age
0 Years
Max age
18 Years
Healthy volunteers
No
Inclusion Criteria:
* All patients affected by Medulloblastoma operated on at the Pediatric Neurosurgery Unit during their pediatric age will be elected to take part to the study
Primary outcome measure(s)
Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6i in MB. — 2 yrs Genetic characterization of PDOs derived from patients with medulloblastoma (MB).
Measurement: Analysis of the mutational status of over 500 genes using TSO-500 sequencing, comparing the genetic profiles of PDOs with those of primary tumors.
Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6i in MB. — 2 years Assessment of changes in cell proliferation in patient-derived organoids (PDOs) from medulloblastoma (MB) treated with CDK4/6 inhibitors compared to untreated controls.
Measurement: Quantified by cell counting assays.
Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6 inhibitors in medulloblastoma (MB). — 2 years Histological characterization of PDOs derived from patients with medulloblastoma (MB).
Measurement: Evaluation of the expression of MB-specific histological markers by immunohistochemistry, comparing expression patterns between PDOs and primary tumors.
Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6i in MB. — 2 years Assessment of changes in cell survival in patient-derived organoids (PDOs) from medulloblastoma (MB) treated with CDK4/6 inhibitors compared to untreated controls.
Measurement: Quantified by cell viability assays.
Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6i in MB. — 2 years Assessment of changes in cellular senescence levels in patient-derived organoids (PDOs) from medulloblastoma (MB) treated with CDK4/6 inhibitors compared to untreated controls.
Measurement: Evaluated by analysis of senescence markers.
Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6i in MB. — 2 years Outcome Measure Title: Quantitative change in cell proliferation Description: Quantitative change in cell proliferation expressed as a percentage variation from baseline.
Unit of Measure: Percent change from baseline (%).
Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6i in MB. — 2 years Outcome Measure Title: Quantitative change in cell survival Description: Quantitative change in cell survival expressed as a percentage variation from baseline.
Unit of Measure: Percent change from baseline (%).
Clarify the molecular mechanisms underlying the acquisition of resistance to CDK4/6i in MB. — 2 years Outcome Measure Title: Quantitative change in cellular senescence Description: Quantitative change in cellular senescence expressed as a percentage variation from baseline.
Unit of Measure: Percent change from baseline (%).
Trial sites (1)
Facility
City
Region
Status
Fondazione Policlinico Gemelli Irccs
Roma
ROMA
Recruiting
More Fondazione Policlinico Universitario Agostino Gemelli IRCCS trials in Italy
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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