2024
Pre-clinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition for low-grade serous ovarian cancer
McNamara B, Greenman M, Demirkiran C, Mutlu L, Hartwich T, Bellone S, Manavella D, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz P, Santin A. Pre-clinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition for low-grade serous ovarian cancer. Gynecologic Oncology 2024, 190: s36. DOI: 10.1016/j.ygyno.2024.07.058.Peer-Reviewed Original ResearchTrastuzumab 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 efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer
McNamara B, Demirkiran C, Hartwich T, Bellone S, Manavella D, Mutlu L, Greenman M, Zipponi M, Yang-Hartwich Y, Yang K, Ratner E, Schwartz P, Coma S, Pachter J, Santin A. Preclinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer. Gynecologic Oncology 2024, 183: 133-140. PMID: 38493021, DOI: 10.1016/j.ygyno.2024.01.028.Peer-Reviewed Original ResearchLow grade serous ovarian carcinomaWhole-exome-sequencingGain-of-function mutationsVS-4718Preclinical efficacyLow grade serous ovarian cancerSerous ovarian cancerControl-treated miceTumor growth inhibitionWild-type KRASLoss of heterozygosityDecreased p-ERKRAF/MEK inhibitionMedian survivalOvarian cancerRecurrence rateTherapeutic optionsOral gavageTumor growthTumor samplesIn vivo activityMAPK pathway genesRAF/MEK inhibitorsP-ERKEx vivo
2020
In vivo modeling of metastatic human high-grade serous ovarian cancer in mice
Kim O, Park EY, Klinkebiel DL, Pack SD, Shin YH, Abdullaev Z, Emerson RE, Coffey DM, Kwon SY, Creighton CJ, Kwon S, Chang EC, Chiang T, Yatsenko AN, Chien J, Cheon DJ, Yang-Hartwich Y, Nakshatri H, Nephew KP, Behringer RR, Fernández FM, Cho CH, Vanderhyden B, Drapkin R, Bast RC, Miller KD, Karpf AR, Kim J. In vivo modeling of metastatic human high-grade serous ovarian cancer in mice. PLOS Genetics 2020, 16: e1008808. PMID: 32497036, PMCID: PMC7297383, DOI: 10.1371/journal.pgen.1008808.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorChromosomal InstabilityCystadenocarcinoma, SerousDEAD-box RNA HelicasesDisease Models, AnimalDNA RepairDrug Resistance, NeoplasmDrug Screening Assays, AntitumorFeasibility StudiesFemaleHumansMiceMice, KnockoutMutationNeoplasm GradingNeoplasm MetastasisOvarian NeoplasmsPeritoneal NeoplasmsPrimary Cell CulturePTEN PhosphohydrolaseRibonuclease IIITumor Suppressor Protein p53ConceptsHigh-grade serous carcinomaHuman HGSCHigh-grade serous ovarian cancerSerous ovarian cancerOvarian cancerPeritoneal metastasisHuman high-grade serous ovarian cancerMetastatic ovarian cancerOvarian cancer typesHuman cancer metastasisHuman cancer mortalityHemorrhagic ascitesClinical metastasisHistopathological similaritiesSerous carcinomaCancer mortalityFallopian tubeMurine modelPeritoneal cavityMouse modelPotential therapyMouse deathMetastasisCancer typesCancer metastasis