Ovarian Cancer
Conditions
Keywords
Ovarian cancer, Resistance, Platinum drug, Parp inhibitors
Brief summary
The project focuses on developing new experimental models of ovarian cancer that accurately reflect patients who do not respond to first-line platinum-based treatments and who are resistant to PARP inhibitors (PARPi). These models are essential for testing new drugs or drug combinations in preclinical settings that closely mimic real clinical conditions. These models will also help to identify predictive biomarkers of treatment response and to better understand the biological mechanisms behind therapy resistance.
Detailed description
The aims of the present project are: * to generate new experimental models from biopsies of ovarian cancer patients whose tumors are either refractory to platinum-based therapy or have relapsed during or after treatment with platinum and PARPi; * molecularly, and pharmacologically characterize these models, including patient-derived xenografts (PDXs) grown in immunodeficient animals, organoids (3D in vitro models) and primary cell cultures (2D) derived from the same biopsies; * to use these models to identify new biomarkers of therapy response, study resistance mechanisms, and design preclinical trials for new therapeutic strategies; The study involves transplanting fresh tumor tissue into immunodeficient mice to create PDX models, as well as generating organoids and cell cultures. It will run for 10 years and include adult female patients (aged 18 or older) with recurrent ovarian cancer treated at the European Institute of Oncology, who have given informed consent. Clinical and pathological data will be collected at enrollment and during follow-up and stored in a coded database.
Interventions
OTHERPlatinum drugs and PARPi
Patients with ovarian carcinoma resistant to platinum drugs and PARPi undergoing paracentasis and/or surgical with left-over tumor material.
Sponsors
Mario Negri Institute for Pharmacological Research
Istituto Europeo di Oncologia
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female patients with malignant ovarian gynecological disease. * Age 18 years or older. * Patients capable of providing informed consent.
Exclusion criteria
-Failure to sign the informed consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To obtain new in vivo experimental models of ovarian carcinomas | 10 years | To obtain new experimental models from biopsies of ovarian carcinomas that are refractory to platinum-based therapy and recurrent during or after treatment with platinum-based therapy and PARP inhibitors, as treated at the Division of Medical Gynecologic Oncology of the European Institute of Oncology. To this end, a portion of the neoplastic tissue will be transplanted subcutaneously into at least two immunodeficient mice and follwed for tumor appearance |
| To obtain new in vitro experimental models of ovarian carcinomas | 10 years | To obtain new experimental models from biopsies of ovarian carcinomas that are refractory to platinum-based therapy and recurrent during or after treatment with platinum-based therapy and PARP inhibitors, as treated at the Division of Medical Gynecologic Oncology of the European Institute of Oncology. To this end, a portion of the neoplastic tissue will digest with collagesase and single cell suspension obtained and seeded with specific mediums suplemented with growth factors in vitro to obtain primary cultures and organoids |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacological characterization of the obtained models: in vivo outcomes | 10 years | The obtained patient derived xenografts (PDX) will be used to test the antitumor activity of platinum drugs and polyADP rybose polymearse inhibitors. The efficiacy of drug treatments will be evaluated calculating the percentage of tumor growth inhibition in mice treated with the anticancer agents compared with untreated controls, assessed by measuring tumor volume (mgr) using a Vernier caliper, following the formula: (Vtreated/Vuntreated)\*100. V=tumor volume |
| Pharmacological characterization of the obtained models: in vitro outcomes | 10 years | In vitro outcomes: IC50 values (50% inhibitory concentration) of different anticancer agents (platinum drugs, PARP inhibitors, and taxanes) evaluated in 3D models and primary cultures using validated cytotoxicity assays. |
| Molecular identification of potential biomarker of response | 10 years | Immunohistochemical (IHC) dection of several proteins in 3D cultures and PDXs models using validated IHC antibodies |
Contacts
CONTACTGiovanna Damia, MD
Outcome results
None listed