0000000000932060

AUTHOR

Gianni Simone

showing 2 related works from this author

Heterogeneity of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer and potential effects on therapy in the CAPRI GOIM trial

2015

Background: Evidence suggests that metastatic colorectal carcinoma (mCRC) has a high level of intratumor heterogeneity. We carried out a quantitative assessment of tumor heterogeneity for KRAS, NRAS, BRAF and PIK3CA mutations, in order to assess potential clinical implications. Patients and methods: Tumor samples (n = 182) from the CAPRI-GOIM trial of first-line cetuximab + FOLFIRI in KRAS exon-2 wild-type mCRC patients were assessed by next-generation sequencing that allows quantitative assessment of mutant genes. Mutant allelic frequency was normalized for the neoplastic cell content and, assuming that somatic mutations usually affect one allele, the Heterogeneity Score (HS) was calculate…

OncologyNeuroblastoma RAS viral oncogene homologOrganoplatinum CompoundsColorectal cancerSettore MED/06 - Oncologia MedicaLeucovorinCetuximabCetuximab; Colorectal cancer; Mutations; Next-generation sequencing; Tumor heterogeneity; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma; Cetuximab; Class I Phosphatidylinositol 3-Kinases; Colorectal Neoplasms; Drug Resistance Neoplasm; Fluorouracil; GTP Phosphohydrolases; Gene Frequency; High-Throughput Nucleotide Sequencing; Humans; Leucovorin; Membrane Proteins; Mutation; Organoplatinum Compounds; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Treatment Outcome; Hematology; OncologyColorectal Neoplasmmedicine.disease_causeGTP PhosphohydrolasesGTP PhosphohydrolasePhosphatidylinositol 3-KinasesGene FrequencyAntineoplastic Combined Chemotherapy ProtocolsMembrane ProteinClass I Phosphatidylinositol 3-KinasecolorectalCetuximabHigh-Throughput Nucleotide SequencingHematologyTreatment OutcomeOncologyFOLFIRIKRASFluorouracilColorectal Neoplasmsmedicine.drugHumanProto-Oncogene Proteins B-rafmedicine.medical_specialtyTumor heterogeneityClass I Phosphatidylinositol 3-KinasesProto-Oncogene Proteins p21(ras)Internal medicinemedicinecancerHumansneoplasmsAllele frequencyAntineoplastic Combined Chemotherapy ProtocolSettore MED/08 - ANATOMIA PATOLOGICAbusiness.industryCarcinomaOrganoplatinum CompoundMembrane ProteinsCancermedicine.diseaseColorectal cancerdigestive system diseasesDrug Resistance NeoplasmMutationCancer researchNext-generation sequencingNeoplastic cellCamptothecinPhosphatidylinositol 3-Kinasebusiness
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KRAS mutations and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal carcinoma: an open issue.

2009

Background: Cetuximab and panitumumab, mAbs targeting EGFR, are registered for metastatic colorectal carcinoma (mCRC) patients whose tumors express EGFR as determined by immunohistochemistry. However, this method is not predictive of treatment efficacy. KRAS, the human homolog of the Kirsten rat sarcoma-2 virus oncogene, encodes a small G-protein that functions downstream of EGFR-induced signalling. Objective/Methods: To examine KRAS mutations as predictive factors of response to anti-EGFR mAbs using recently published data. Results/conclusions: Several retrospective studies show that efficacy of these mAbs is confined to patients with wild type KRAS and genotyping of tumors should be consi…

Oncologymedicine.medical_specialtymedicine.drug_classColorectal cancerClinical BiochemistryPopulationCetuximabMonoclonal antibodymedicine.disease_causeAntibodies Monoclonal HumanizedProto-Oncogene Proteins p21(ras)Internal medicineProto-Oncogene ProteinsDrug DiscoverymedicinePanitumumabAnimalsHumansKRAScolorectal carcinomaeducationneoplasmsGenotypingPharmacologyeducation.field_of_studyClinical Trials as TopicCetuximabbusiness.industryPanitumumabAntibodies Monoclonalmedicine.diseasedigestive system diseasesErbB ReceptorsMutationCancer researchras ProteinsImmunohistochemistryKRASbusinessColorectal Neoplasmsmedicine.drugExpert opinion on biological therapy
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