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dc.contributor.advisorDel Mastro, Lucia <1964>
dc.contributor.authorMartelli, Valentino <1991>
dc.contributor.otherClara Montagut
dc.date.accessioned2023-11-16T15:24:20Z
dc.date.available2023-11-16T15:24:20Z
dc.date.issued2023-11-14
dc.identifier.urihttps://unire.unige.it/handle/123456789/6960
dc.description.abstractBackground: Nel trattamento del carcinoma del colon-retto metastatico (mCRC), è cruciale identificare biomarcatori predittivi per terapie specifiche, come l'instabilità dei microsatelliti per l'immunoterapia, le mutazioni RAS/RAF per inibitori dell'EGFR (cetuximab) e la mutazione BRAFV600E per encorafenib e cetuximab. La biopsia liquida è un'alternativa quando la biopsia tissutale è invasiva o ritardata. Purpose: Questa seconda analisi dello studio PLATFORM-B esamina le mutazioni troncali e le mutazioni secondarie nel ctDNA al momento della progressione della malattia per comprendere le dinamiche di resistenza alle terapie anti-EGFR e la progressione del mCRC. Experimental design: Il ctDNA al baseline e alla progressione è stato analizzato tramite next-generation sequencing (NGS). Le mutazioni troncali sono state considerate come biomarcatori del carico tumorale totale, mentre le mutazioni RAS/BRAF/MEK/EGFR-ECD come mutazioni di resistenza. I risultati del ctDNA sono stati correlati agli outcome clinici. Results: Al momento della stesura, le analisi dei campioni di plasma sono completate, ma le analisi statistiche sono ancora in corso. Pertanto, vengono riportati risultati parziali e preliminari. Conclusions: Questo studio potrà fornire nuove intuizioni sui meccanismi di resistenza alle terapie di prima linea con anti-EGFR nel mCRC.it_IT
dc.description.abstractBackground: The treatment of metastatic colorectal cancer (mCRC) requires testing three prognostic and predictive biomarkers on tumor tissue samples: microsatellite instability status and mutations in the RAS and BRAF genes. Patients with RAS/BRAF wild-type (wt) tumors benefit from adding to chemotherapy monoclonal antibodies (mAbs) that inhibit the activation of the epidermal growth factor receptor (EGFR) -cetuximab and panitumumab. Circulating tumor DNA (ctDNA) analysis through liquid biopsy is a valuable alternative for genotyping tumor biomarkers, since it is less “invasive” than tissue biopsy and its reporting times are relatively short. PLATFORM-B was the first study to demonstrate the role of ctDNA in predicting the response to first-line chemotherapy plus Cetuximab in mCRC patients with RAS wt tumors. Purpose: This second analysis of the PLATFORM-B study evaluates changes over time in trunk mutations and secondary mutations found in liquid biopsies at disease progression. The aim is to better understand the dynamics of resistance to anti-EGFR therapies and the mechanisms behind the progression of mCRC tumors. Experimental design: ctDNA at baseline and progression was analyzed using next-generation sequencing (NGS). Trunk mutations were considered as surrogate biomarkers for the total tumor burden, while RAS/BRAF/MEK/EGFR-ECD mutations were considered resistance mutations. The ctDNA results were subsequently correlated with clinical outcomes. Results: As of the writing of this work, plasma sample analyses have been completed, but statistical analyses are still in progress. Therefore, the text reports partial and preliminary results. Conclusions: ctDNA analysis will make patient selection more accurate, minimizing the risk of unnecessary toxicity from ineffective treatments, thanks to a better understanding of tumor dynamics and the mechanisms of resistance to anti-EGFR.en_UK
dc.language.isoen
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.titleRuolo della biopsia liquida nella malattia colorettale metastatica trattata con chemioterapia di I linea in associazione ad anti-EGFR: analisi dello studio PLATFORM-Bit_IT
dc.title.alternativeThe role of liquid biopsy in metastatic colorectal cancer treated with first-line chemotherapy plus anti-EGFR: analysis of the study PLATFORM-Ben_UK
dc.typeinfo:eu-repo/semantics/doctoralThesis
dc.subject.miurMED/06 - ONCOLOGIA MEDICA
dc.publisher.nameUniversità degli studi di Genova
dc.date.academicyear2021/2022
dc.description.corsolaurea10271 - ONCOLOGIA MEDICA
dc.description.area6 - MEDICINA E CHIRURGIA
dc.description.department100007 - DIPARTIMENTO DI MEDICINA INTERNA E SPECIALITÀ MEDICHE
dc.description.doctoralThesistypeScuola di Specializzazione


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