Establishment of novel cell lines recapitulating the genetic landscape of uveal melanoma and preclinical validation of mTOR as a therapeutic target

摘要: Uveal melanoma (UM) is the most common primary tumor of eye in adults. There no standard adjuvant treatment to prevent metastasis and effective therapy metastatic setting. We have established a unique panel 7 UM cell lines from either patient's tumors or patient-derived xenografts (PDXs). This recapitulates molecular landscape disease terms genetic alterations mutations. All display GNAQ GNA11 activating mutations, importantly four them BAP1 (BRCA1 associated protein-1) deficiency, hallmark aggressive disease. The mTOR pathway was shown be activated independent AKT signaling. inhibitor Everolimus reduced viability significantly delayed growth 4 PDXs. Our data suggest that inhibition with Everolimus, possibly combination other agents, may considered as therapeutic option for management uveal melanoma.