2024
Targeting DHX9 triggers tumor-intrinsic interferon response and replication stress in Small Cell Lung Cancer
Murayama T, Nakayama J, Jiang X, Miyata K, Morris A, Cai K, Prasad R, Ma X, Efimov A, Belani N, Gerstein E, Tan Y, Zhou Y, Kim W, Maruyama R, Campbell K, Chen L, Yang Y, Balachandran S, Canadas I. Targeting DHX9 triggers tumor-intrinsic interferon response and replication stress in Small Cell Lung Cancer. Cancer Discovery 2024, 14: 468-491. PMID: 38189443, PMCID: PMC10905673, DOI: 10.1158/2159-8290.cd-23-0486.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerDExD/H-box helicase 9Cell lung cancerCold tumorsLung cancerResponse to immune-checkpoint blockadeInnate immunityEnhance immunotherapy efficacyImmune-checkpoint blockadeImmunogenic tumor microenvironmentImmunologically cold tumorsNucleic acid-sensing pathwaysActivate innate immunityAntitumor immunityImmunotherapy efficacyReplication stressTumor microenvironmentTumor growthViral mimicryTumorImmune responseCancer cellsInterferon responseCytoplasmic dsRNACancer
2019
The multikinase inhibitor RXDX-105 is effective against neuroblastoma in vitro and in vivo
Flynn S, Lesperance J, Macias A, Phanhthilath N, Paul M, Kim J, Tamayo P, Zage P. The multikinase inhibitor RXDX-105 is effective against neuroblastoma in vitro and in vivo. Oncotarget 2019, 10: 6323-6333. PMID: 31695841, PMCID: PMC6824878, DOI: 10.18632/oncotarget.27259.Peer-Reviewed Original ResearchRXDX-105Small molecule inhibitor of multiple kinasesPediatric cancer-related deathsExtracranial solid tumor of childhoodSolid tumor of childhoodHigh riskHigh-risk neuroblastomaInhibitor of multiple kinasesTumor of childhoodNeuroblastoma in vitroExtracranial solid tumorTreatment of neuroblastoma cellsCancer-related deathsNeuroblastoma cellsRelapsed neuroblastomaRelapsed tumorsMaintenance therapyCell cycle arrestXenograft tumorsTumor growthSmall molecule inhibitorsRas-MAPK pathwayCombined inhibitionRET phosphorylationTumorModelling bistable tumour population dynamics to design effective treatment strategies
Akhmetzhanov A, Kim J, Sullivan R, Beckman R, Tamayo P, Yeang C. Modelling bistable tumour population dynamics to design effective treatment strategies. Journal Of Theoretical Biology 2019, 474: 88-102. PMID: 31077681, PMCID: PMC9534689, DOI: 10.1016/j.jtbi.2019.05.005.Peer-Reviewed Original ResearchConceptsDrug resistanceHeterogeneous tumorsTumor cellsTreatment strategiesDevelopment of optimal therapeutic strategiesEffects of targeted drugsBRAF-mutant melanomaProcess of tumor growthOptimal therapeutic strategyDrug resistance characteristicsHeterogeneous tumor cellsReverse drug resistanceActivated alternative pathwayEmergence of resistanceCancer treatment modalityEffective treatment strategiesDesigning effective treatment strategiesDrug holidayBRAF inhibitorsPeriodate treatmentDrug regimensTreatment modalitiesGenetic alterationsTumor growthDrug sensitivity