​Establishment and molecular characterization of preclinical models of aggressive gynecologic cancer​

Project aims

  1. ​​​To molecularly characterize aggressive gynecologic tract cancer with parallel preclinical ex vivo or in vivo model development 
  2. To subject these preclinical models to high throughput drug screen and to targeted drug evaluation as informed by the results of the molecular characterization 

 

Summary

This study will focus on clinically aggressive types of gynecologic tract (ovary and endometrium) cancer in which more effective systemic therapy options are urgently needed. These include for instances high-grade serous tubo-ovarain carcinoma (HGSC), low-grade serous ovarian carcinoma (LGSC), ovarian adult granulosa cell tumor (AGCT), ovarian/endometrial undifferentiated/dedifferentiated carcinoma (UC) and carcinosarcoma (CS). The primary study aim is to develop preclinical patient tumor-derived experimental models (in vitro 3D cell line and in vivo patient derived xenograft models) for these tumor types and subject the in vitro models to high throughput drug repurposing screen and CRISPR screen to gain therapeutic insights, followed by further validation in corresponding in vivo models for promising candidate drug(s)/target(s). The results of TFRI-sponsored molecular characterization will be correlated with these therapeutically oriented screens and to inform on specific targeted therapy opportunity. 

 

Anticipated outcomes and impact

​​We anticipate that the drug and/or CRISPR screen on these patient-derived ex vivo models will lead to the identification of candidate drugs or drug targets for the treatment of the corresponding aggressive gynecologic tract cancer, and that the molecular analyses performed with TFRI support will not only enable us to prioritize candidte drugs/targets and to inform on additional targetable alterations based on the respective genomic mutation and gene expression landscapes of the tumors. This will ultimately lead to the development of more treatment options for patients afflicted by these aggressive gynecologic tract cancer that lack effective treatment options at the present.