2024
Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors
Choi Y, Dharia N, Jun T, Chang J, Royer-Joo S, Yau K, Assaf Z, Aimi J, Sivakumar S, Montesion M, Sacher A, LoRusso P, Desai J, Schutzman J, Shi Z, group A. Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors. Clinical Cancer Research 2024, 30: of1-of10. PMID: 38995268, PMCID: PMC11369623, DOI: 10.1158/1078-0432.ccr-24-0255.Peer-Reviewed Original ResearchConceptsKRAS G12C mutationTumor fractionSolid tumorsTumor typesG12C mutationOn-treatment time pointsNon-small cell lung cancerMutational heterogeneityAssociated with tumor typeProgression-free survivalPlasma samplesPhase 1 studyCell lung cancerCycle 1 dayAssociated with patient outcomesVariant allele frequencyAssociated with responseCtDNA levelsCtDNA profilingMetastatic sitesTruncal mutationsTumor DNATreatment responseLung cancerTumor tissuesUnlocking the Potential: Biomarkers of Response to Antibody-Drug Conjugates.
Ascione L, Guidi L, Prakash A, Trapani D, LoRusso P, Lou E, Curigliano G. Unlocking the Potential: Biomarkers of Response to Antibody-Drug Conjugates. American Society Of Clinical Oncology Educational Book 2024, 44: e431766. PMID: 38828973, DOI: 10.1200/edbk_431766.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBiomarkers, TumorDrug Resistance, NeoplasmHumansImmunoconjugatesMolecular Targeted TherapyNeoplasmsTreatment OutcomeConceptsAntibody-drug conjugatesTumor sitePredictive biomarkersAntigen expressionLack of robust predictive biomarkersSelection of targeted therapiesRobust predictive biomarkersTarget antigen expressionTumor antigen expressionCancer treatment landscapeBiomarkers of responseImprove patient selectionTumor intrinsic featuresBiomarkers of safetyUnique adverse eventsIdentification of patientsPopulation of patientsClinically actionable biomarkersSmall-molecule agentsPatient-centred outcomesTreatment landscapeBiomarker-drivenTreatment resistanceClinical benefitPatient selectionCirculating Tumor DNA Dynamics Fail to Predict Efficacy of Poly(ADP-ribose) Polymerase/VEGFR Inhibition in Patients With Heavily Pretreated Advanced Solid Tumors
Hu Y, Narayan A, Xu Y, Wolfe J, Vu D, Trinh T, Kantak C, Ivy S, Eder J, Deng Y, LoRusso P, Kim J, Patel A. Circulating Tumor DNA Dynamics Fail to Predict Efficacy of Poly(ADP-ribose) Polymerase/VEGFR Inhibition in Patients With Heavily Pretreated Advanced Solid Tumors. JCO Precision Oncology 2024, 8: e2300289. PMID: 38412387, PMCID: PMC10914240, DOI: 10.1200/po.23.00289.Peer-Reviewed Original ResearchConceptsCell-free circulating tumor DNANon-small-cell lung cancerSmall-cell lung cancerTriple-negative breast cancerPancreatic ductal adenocarcinomaAdvanced solid tumorsVariant allele fractionRadiographic responseOverall survivalCombination therapySolid tumorsCtDNA levelsLung cancerPretreated advanced solid tumorsDays of combination therapyMetastatic pancreatic ductal adenocarcinomaResponse to anticancer therapyAssociated with disease progressionProgression-free survivalPlasma samplesLead-inPoly(ADP-riboseInferior OSTumor DNASurvival outcomes
2023
Genome-wide analysis of aberrant position and sequence of plasma DNA fragment ends in patients with cancer
Budhraja K, McDonald B, Stephens M, Contente-Cuomo T, Markus H, Farooq M, Favaro P, Connor S, Byron S, Egan J, Ernst B, McDaniel T, Sekulic A, Tran N, Prados M, Borad M, Berens M, Pockaj B, LoRusso P, Bryce A, Trent J, Murtaza M. Genome-wide analysis of aberrant position and sequence of plasma DNA fragment ends in patients with cancer. Science Translational Medicine 2023, 15: eabm6863. PMID: 36630480, PMCID: PMC10080578, DOI: 10.1126/scitranslmed.abm6863.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCell-Free Nucleic AcidsChromatinDNAHumansNeoplasmsNucleotidesSequence Analysis, DNAConceptsGenome-wide analysisNucleotide frequenciesDNA fragmentsGenome-wide differencesFragment endsNovel cancer diagnosticsCopy number amplificationChromatin accessibilityGenomic regionsGenomic positionsGC contentDNA sequencesSequencing dataDifferent cancer typesNumber amplificationCell typesCellular originSomatic mutationsCancer cellsFragment lengthCell-free DNADNACancer typesFragmentsSequence
2022
First in Human Phase 1/2 ICONIC Trial of the ICOS agonist vopratelimab alone and with nivolumab: ICOS high CD4 T cell populations and predictors of response
Yap TA, Gainor JF, Callahan MK, Falchook GS, Pachynski RK, LoRusso P, Kummar S, Gibney GT, Burris HA, Tykodi SS, Rahma OE, Seiwert TY, Papadopoulos KP, Murphy M, Park H, Hanson A, Hashambhoy-Ramsay Y, McGrath L, Hooper E, Xiao X, Cohen H, Fan M, Felitsky D, Hart C, McComb R, Brown K, Sepahi A, Jimenez J, Zhang W, Baeck J, Laken H, Murray R, Trehu E, Harvey CJ. First in Human Phase 1/2 ICONIC Trial of the ICOS agonist vopratelimab alone and with nivolumab: ICOS high CD4 T cell populations and predictors of response. Clinical Cancer Research 2022, 28: 3695-3708. PMID: 35511938, PMCID: PMC9433959, DOI: 10.1158/1078-0432.ccr-21-4256.Peer-Reviewed Original ResearchConceptsSubset of patientsPredictive biomarkersPharmacodynamic biomarkersModest objective response rateNon-small cell lung cancer trialsCD4 T cell populationCell lung cancer trialsPhase IObjective response ratePhase II doseAdvanced solid tumorsCD4 T cellsFavorable safety profilePotential predictive biomarkersLung cancer trialsPredictors of responseT cell populationsGreater clinical benefitClinical outcomesClinical benefitSafety profileCancer trialsNivolumabT cellsPatients
2019
Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors
Jung KH, LoRusso P, Burris H, Gordon M, Bang YJ, Hellmann MD, Cervantes A, de Olza M, Marabelle A, Hodi FS, Ahn MJ, Emens LA, Barlesi F, Hamid O, Calvo E, McDermott D, Soliman H, Rhee I, Lin R, Pourmohamad T, Suchomel J, Tsuhako A, Morrissey K, Mahrus S, Morley R, Pirzkall A, Davis SL. Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors. Clinical Cancer Research 2019, 25: 3220-3228. PMID: 30770348, PMCID: PMC7980952, DOI: 10.1158/1078-0432.ccr-18-2740.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorHumansImidazolesIndoleamine-Pyrrole 2,3,-DioxygenaseIndolesMagnetic Resonance ImagingMiddle AgedNeoplasm MetastasisNeoplasm StagingNeoplasmsTomography, X-Ray ComputedTreatment OutcomeConceptsPD-L1 inhibitorsT cellsPartial responseAdvanced cancerDay 1Dose levelsCommon treatment-related AEsDose-escalation stageTreatment-related AEsAdvanced solid tumorsEffector T cellsRegulatory T cellsLinear pharmacokinetic profileLocal tumor microenvironmentInvestigational small-molecule inhibitorExpansion patientsKynurenine accumulationComplete responseImmune suppressionIntravenous infusionAcceptable safetyTryptophan depletionNavoximodAtezolizumabPlasma Kyn
2014
AN INTEGRATED FRAMEWORK FOR REPORTING CLINICALLY RELEVANT BIOMARKERS FROM PAIRED TUMOR/NORMAL GENOMIC AND TRANSCRIPTOMIC SEQUENCING DATA IN SUPPORT OF CLINICAL TRIALS IN PERSONALIZED MEDICINE
Altman R, Dunker A, Hunter L, Ritchie M, Murray T, Klein T, NASSER S, KURDOGLU A, IZATT T, ALDRICH J, RUSSELL M, CHRISTOFORIDES A, TEMBE W, KIEFER J, CORNEVEAUX J, BYRON S, FORMAN K, ZUCCARO C, KEATS J, LORUSSO P, CARPTEN J, TRENT J, CRAIG D. AN INTEGRATED FRAMEWORK FOR REPORTING CLINICALLY RELEVANT BIOMARKERS FROM PAIRED TUMOR/NORMAL GENOMIC AND TRANSCRIPTOMIC SEQUENCING DATA IN SUPPORT OF CLINICAL TRIALS IN PERSONALIZED MEDICINE. Biocomputing 2014, 56-67. PMID: 25592568, DOI: 10.1142/9789814644730_0007.Peer-Reviewed Original ResearchConceptsTranscriptomic sequencing dataHigh-throughput genomic dataRelational database systemsTerabytes of dataTumor/normal samplesSingle nucleotide changeDiversity of usersReal-time mannerIndividual genomesAnnotation databasesDatabase systemsFlexible computational frameworkChromosomal rearrangementsGenomic dataGene expressionSequencing dataData structureComputational architectureGene fusionsNucleotide changesMultiple trackersBase pairsSmall insertionsTime mannerClinical genomic testing
1996
Levels of 5‐hydroxymethyl‐2′‐deoxyuridine in DNA from blood as a marker of breast cancer
Djuric Z, Heilbrun L, Simon M, Smith D, Luongo D, LoRusso P, Martino S. Levels of 5‐hydroxymethyl‐2′‐deoxyuridine in DNA from blood as a marker of breast cancer. Cancer 1996, 77: 691-696. PMID: 8616761, DOI: 10.1002/(sici)1097-0142(19960215)77:4<691::aid-cncr15>3.0.co;2-w.Peer-Reviewed Original Research