2024
Preclinical evaluation of avutometinib and defactinib in high‐grade endometrioid endometrial cancer
Hartwich T, Mansolf M, Demirkiran C, Greenman M, Bellone S, McNamara B, Nandi S, Alexandrov L, Yang‐Hartwich Y, Coma S, Pachter J, Santin A. Preclinical evaluation of avutometinib and defactinib in high‐grade endometrioid endometrial cancer. Cancer Medicine 2024, 13: e70210. PMID: 39240189, PMCID: PMC11378359, DOI: 10.1002/cam4.70210.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBenzamidesCarcinoma, EndometrioidCell Line, TumorCell ProliferationEndometrial NeoplasmsExome SequencingFemaleFocal Adhesion Kinase 1HumansImidazolesMiceNeoplasm GradingOxazepinesProtein Kinase InhibitorsPyrazinesSulfonamidesXenograft Model Antitumor AssaysConceptsFocal adhesion kinaseWhole-exome sequencingEndometrial cancer cell linesVS-4718Cell linesRas/MAPK pathwayPhosphorylated focal adhesion kinaseWestern blot assayWhole-exome sequencing resultsRAF/MEK inhibitionEAC cell linesBlot assayP-FAKGenetic landscapeCell cycleEndometrial cancerGenetic derangementsDefactinibP-MEKGrowth inhibitionRAF/MEKRas/MAPKCell viabilityP-ERKHigh-grade endometrial cancer
2021
A Benzenesulfonamide-based Mitochondrial Uncoupler Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Epithelial Ovarian Cancer
Bi F, Jiang Z, Park W, Hartwich TMP, Ge Z, Chong KY, Yang K, Morrison MJ, Kim D, Kim J, Zhang W, Kril LM, Watt DS, Liu C, Yang-Hartwich Y. A Benzenesulfonamide-based Mitochondrial Uncoupler Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Epithelial Ovarian Cancer. Molecular Cancer Therapeutics 2021, 20: molcanther.mct-21-0396-a.2021. PMID: 34625503, PMCID: PMC8643344, DOI: 10.1158/1535-7163.mct-21-0396.Peer-Reviewed Original ResearchConceptsEpithelial ovarian cancerImmunogenic cell deathOvarian cancerTumor progressionAntitumor adaptive immune responsesDamage-associated molecular patternsCancer cellsMitochondrial uncouplerAdaptive immune responsesOvarian cancer modelCause of deathCurrent chemotherapeutic agentsNew therapeutic strategiesOvarian cancer cellsCancer cell proliferationCell deathEndoplasmic reticulum stressGynecologic malignanciesClinical outcomesEndoplasmic reticulum stress sensorNew anticancer therapiesPeritoneal fluidInduces Endoplasmic Reticulum StressImmune responseAbdominal cavity
2019
An Underlying Mechanism of Dual Wnt Inhibition and AMPK Activation: Mitochondrial Uncouplers Masquerading as Wnt Inhibitors
Zhang W, Sviripa VM, Kril L, Yu T, Xie Y, Hubbard W, Sullivan P, Chen X, Zhan CG, Yang-Hartwich Y, Evers BM, Spear B, Gedaly R, Watt DS, Liu C. An Underlying Mechanism of Dual Wnt Inhibition and AMPK Activation: Mitochondrial Uncouplers Masquerading as Wnt Inhibitors. Journal Of Medicinal Chemistry 2019, 62: 11348-11358. PMID: 31774672, PMCID: PMC7560992, DOI: 10.1021/acs.jmedchem.9b01685.Peer-Reviewed Original Research