Sarcomatoid Dedifferentiation in Renal Cell Carcinoma: From Novel Molecular Insights to New Clinical Opportunities.
Fiche publication
Date publication
décembre 2019
Journal
Cancers
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BARTHELEMY Philippe, Pr LANG Hervé, Dr LINDNER Véronique, Pr MALOUF Gabriel
Tous les auteurs :
Debien V, Thouvenin J, Lindner V, Barthélémy P, Lang H, Flippot R, Malouf GG
Lien Pubmed
Résumé
Sarcomatoid features in renal cell carcinoma (RCC) have long been associated with dismal prognosis and poor response to therapy, while biological mechanisms underpinning sarcomatoid dedifferentiation remained obscure. Several efforts have been conducted to break down the molecular profile of sarcomatoid RCC and investigate different targeted therapeutic approaches. Mutations enriched for in sarcomatoid RCC involve, notably, , , cell cycle, and chromatin-remodeling genes. The immunological landscape of these tumors is also gradually being uncovered, showing frequent expression of programmed cell death ligand-1 (PD-L1) and high levels of tumor-infiltrating lymphocytes. These features may be major determinants for the activity of immune checkpoint inhibitors in this population, which has been confirmed by retrospective studies and subgroup analyses of large randomized phase 3 trials. Combinations based on PD-1/PD-L1 inhibition have demonstrated response rates and complete responses in >50% and >10% of patients in the first-line metastatic setting, respectively, with median overall survival exceeding two years. This remarkable improvement in outcomes effectively establishes immune checkpoint inhibitor combinations as a new standard of care in patients with sarcomatoid RCC. New research fields, including epigenetic regulations and tumor-microenvironment interactions, may further sharpen understanding of sarcomatoid RCC and advance therapeutic developments.
Mots clés
immunotherapy, renal cell carcinoma, sarcomatoid
Référence
Cancers (Basel). 2019 Dec 31;12(1):