Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2
Mutlu L, McNamara B, Bellone S, Manavella D, Demirkiran C, Greenman M, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2. Clinical & Experimental Metastasis 2024, 41: 765-775. PMID: 38909139, DOI: 10.1007/s10585-024-10297-z.Peer-Reviewed Original ResearchHigh-grade serous ovarian cancerClear cell carcinomaHER2-targeting antibody-drug conjugateAntibody-drug conjugatesT-DXdReceptor over-expressionTrastuzumab deruxtecanXenograft modelCell linesOvarian clear cell carcinomaOvarian cancer cell linesTumors overexpressing HER2Biologically aggressive tumorsFluorescence in situ hybridization assaySerous ovarian cancerEffective antibody-drug conjugatesIn vivo antitumor activityMouse xenograft modelMetastatic cell linesDS-8201aCancer cell linesAggressive tumorsHER2 expressionCell carcinomaOvarian cancerPreclinical in vitro and in vivo activity of the RAF/MEK clamp avutometinib in combination with FAK inhibition in uterine carcinosarcomas
Demirkiran C, Greenman M, Bellone S, McNamara B, Hartwich T, Manavella D, Mutlu L, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz P, Coma S, Pachter J, Santin A. Preclinical in vitro and in vivo activity of the RAF/MEK clamp avutometinib in combination with FAK inhibition in uterine carcinosarcomas. Gynecologic Oncology 2024, 187: 12-20. PMID: 38703673, DOI: 10.1016/j.ygyno.2024.04.010.Peer-Reviewed Original ResearchFocal adhesion kinaseUC cell linesWhole-exome-sequencingFAK inhibitorCell linesFocal adhesion kinase inhibitionPhosphorylated (p)‑FAKWestern blot assayRAF/MEK inhibitionUterine carcinosarcomaRAS/MAPK pathway genesPreclinical in vitroBlot assayVS-4718Cell cycle assayGenetic landscapePathway genesMAP2KGenetic alterationsDecreased p-ERKCycle assaySuperior tumor growth inhibitionBiologically aggressive tumorsGrowth inhibitionIn vitro activity