Advancing gastric cancer precision medicine in Latinos through patient-derived modeling
Advancing gastric cancer precision medicine in Latinos through patient-derived modeling
批准号:
10733395
负责人:
Luis Guillermo Carvajal Carmona
金额:
$31.79万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-08-01 至 2028-07-31
关键词:
AddressAfrican AmericanBiological AssayCaliforniaCancer BurdenCancer EtiologyCancer ModelCancer PatientCancer Therapy Evaluation ProgramCell CycleChemotherapy-Oncologic ProcedureClinical ResearchClinical TrialsCollectionComplexComprehensive Cancer CenterDataDevelopmentDiagnosisDisparityDrug CombinationsDrug ModelingsEthnic OriginEthnic PopulationEuropeanFDA approvedFRAP1 geneFrequenciesFundingGenerationsGenesGeneticGenomeGenomicsGoalsHigh PrevalenceIn VitroIncidenceIndigenous AmericanInfrastructureKnowledgeLatina PopulationLatinoLatino PopulationLung NeoplasmsMalignant NeoplasmsMedicineMinorityMinority GroupsModelingMolecular TargetMutateMutationOrganoidsPI3K/AKTPIK3CA genePIK3CG genePathway interactionsPatientsPatternPharmaceutical PreparationsPhosphotransferasesPopulationRaceReceptor Protein-Tyrosine KinasesResearchResearch PersonnelResistanceSignal PathwaySomatic MutationStomach NeoplasmsTestingTexasThe Cancer Genome AtlasTranslatingTranslational ResearchUniversitiesWomanWorkcancer genomecancer genomicscancer health disparitycancer therapycancer typecandidate identificationcandidate markerchemotherapyethnic minorityexome sequencinggenomic datahigh riskin vivoinhibitorkinase inhibitormalemalignant stomach neoplasmmenminority patientmolecular subtypesmortalitymortality disparitymutantnovel drug combinationnovel therapeuticspatient derived xenograft modelpre-clinicalprecision medicineprecision oncologyracial minorityracial populationrepositoryresponsesurvival disparitytargeted cancer therapytargeted therapy trialstargeted treatmenttreatment responsetumortumor growth
中文摘要
项目总结/ ASTRACT
英文摘要
PROJECT SUMMARY/ASTRACT
Gastric cancer (GC) is a leading cause of cancer incidence, mortality, and survival disparities in Latinos, the
largest and youngest U.S. minority and the largest racial/ethnic group in the UCaTS states of California and
Texas. When compared to non-Latino whites (NLW), GC incidence and mortality is ~>2-fold higher in Latinos.
Indeed, among all cancer types, GC is the malignancy with the highest disparity ratio among Latinos. Latinas
have a 2.6-fold higher GC mortality compared to NLW women, while Latino men are at a 2.1.-fold higher risk of
dying when diagnosed with GC relative to NLW men. Despite this high GC burden and the fact that most gastric
tumors carry “druggable” mutations, only three targeted therapies have been approved for GC. As part of our
ongoing UCaMP (University of California Minority Patient-Derived Xenograft Development and Trial) minority-
focused PDTC, we have shown that most GC molecular subtypes in Latinos carry druggable mutations and that
they are particularly enriched in tumors carrying multiple and complex genome alterations in PI3K/AKT/mTOR,
CDK, WNT, and RTK/RAS pathway genes. Over half of Latino tumors have mutations in multiple genes in these
and other pathways. Because ~35% of Latino GCs have dual/concurrent PI3K and CDK pathway alterations, we
will initially focus our studies using these two pathways but will aim to expand to other type of tumors with co-
mutated pathways. This project aims to develop a body of pre-clinical and mechanistic data that will help address
Latino GC disparities, and that will be necessary for the establishment of minority-focused clinical trials of
targeted therapies. As part of our NCI-funded UCaMP PDTC, our UCaTS research team has already successfully
created 55 patient-derived GC models, with ~60% of the models from Latinos. We have also shown that Latino
PDXs are responsive to dual treatments with PI3K inhibitors (PI3Ki) and CDK inhibitors (CDKi) and have
identified a model with PIK3CA hotspot mutations with an exquisite response to the PIK3i taselisib. Using our
UCaTS infrastructure of six comprehensive cancer centers in California and Texas, our goal in the next cycle of
our U54 study is to establish an additional 60 GC models, all from minorities, and to work on the following aims:
i) To evaluate GC patient-derived models for identifying efficacious drug combination in tumors with multiple
pathway alterations; ii) To understand the mechanisms of response to taselisib in PIK3CA mutant tumors and;
iii) To evaluate the effect of genetic ancestry in response to chemotherapies and targeted therapies in Latinos.
Through these studies we will develop effective drug combinations that can be rapidly translated into minority-
focused clinical trials for gastric cancer patients.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
University of California and UT Southwestern D-PDTC
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批准号:10733391
-
项目类别:
-
资助金额:$106.11万
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财政年份:2023
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负责人:Luis Guillermo Carvajal Carmona
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依托单位:
Admin Core
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批准号:10733392
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项目类别:
-
资助金额:$22.65万
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财政年份:2023
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负责人:Luis Guillermo Carvajal Carmona
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依托单位:
Preclinical studies of KRAS and EGFR mutations in lung cancer PDXs
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批准号:10582478
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项目类别:
-
资助金额:$20.0万
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财政年份:2022
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负责人:Luis Guillermo Carvajal Carmona
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依托单位:
UC Davis Multi-Disciplinary Cancer Research Training Program to Advance Precision Cancer Prevention and Care in Latin America.
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批准号:10438437
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项目类别:
-
资助金额:$27.0万
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财政年份:2022
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负责人:Luis Guillermo Carvajal Carmona
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依托单位:
Bridges to Doctorate Program between Fresno State and UC Davis
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批准号:10674976
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项目类别:
-
资助金额:$27.4万
-
财政年份:2020
-
负责人:Luis Guillermo Carvajal Carmona
-
依托单位:
Bridges to Doctorate Program between Fresno State and UC Davis
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批准号:10223383
-
项目类别:
-
资助金额:$32.38万
-
财政年份:2020
-
负责人:Luis Guillermo Carvajal Carmona
-
依托单位:
Bridges to Doctorate Program between Fresno State and UC Davis
-
批准号:10024812
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项目类别:
-
资助金额:$12.36万
-
财政年份:2020
-
负责人:Luis Guillermo Carvajal Carmona
-
依托单位:
Bridges to Doctorate Program between Fresno State and UC Davis
-
批准号:10454971
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项目类别:
-
资助金额:$26.88万
-
财政年份:2020
-
负责人:Luis Guillermo Carvajal Carmona
-
依托单位:
Development of Research And Writing Skills (DRAWS): A tool for broader assessment to enhance research and research training
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批准号:10393926
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项目类别:
-
资助金额:$0.67万
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财政年份:2020
-
负责人:Luis Guillermo Carvajal Carmona
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依托单位:
University of California Minority Patient-Derived Xenograft (PDX) Development and Trial Center (UCaMP) to Reduce Cancer Health Disparities
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批准号:10011077
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项目类别:
-
资助金额:$1.2万
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财政年份:2018
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负责人:Luis Guillermo Carvajal Carmona
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依托单位:
Genetic studies of homologous recombination deficiency in hispanic gastric cancer
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批准号:10172867
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项目类别:
-
资助金额:$52.7万
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财政年份:2018
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负责人:Luis Guillermo Carvajal Carmona
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依托单位:
Genetic studies of homologous recombination deficiency in hispanic gastric cancer
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批准号:10411392
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项目类别:
-
资助金额:$7.26万
-
财政年份:2018
-
负责人:Luis Guillermo Carvajal Carmona
-
依托单位:
Genetic studies of homologous recombination deficiency in hispanic gastric cancer
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批准号:10425289
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项目类别:
-
资助金额:$38.08万
-
财政年份:2018
-
负责人:Luis Guillermo Carvajal Carmona
-
依托单位:
Genetic studies of homologous recombination deficiency in hispanic gastric cancer
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批准号:10524102
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项目类别:
-
资助金额:$1.11万
-
财政年份:2018
-
负责人:Luis Guillermo Carvajal Carmona
-
依托单位:
University of California Minority Patient-Derived Xenograft (PDX) Development and Trial Center (UCaMP) to Reduce Cancer Health Disparities
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批准号:9905142
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项目类别:
-
资助金额:$32.29万
-
财政年份:2018
-
负责人:Luis Guillermo Carvajal Carmona
-
依托单位:
Genetic studies of homologous recombination deficiency in hispanic gastric cancer
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批准号:10578426
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项目类别:
-
资助金额:$5.91万
-
财政年份:2018
-
负责人:Luis Guillermo Carvajal Carmona
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依托单位:
Dissecting gastric cancer clonality with genomic analyses and patient xenografts
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批准号:9188431
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项目类别:
-
资助金额:$17.07万
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财政年份:2016
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负责人:Luis Guillermo Carvajal Carmona
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依托单位:
海外基金