Exploiting microRNAs as circulating biomarkers and regulators of key targetable proteins to combat cancer chemoresistance
The limited availability of effe ctive treatments and the generally poor prognosis associated with man y cancer types highlight the pressing need for novel therapeutic appr oaches and new directions in chemoresistance research. Accordingly, t his thesis aims to elucidate the mechanisms driving the development o f chemoresistance and to identify potential vulnerabilities that may be exploited to improve the effectiveness of chemotherapy. Specifical ly, this work examines the role of microRNAs (miRNAs) in therapy resi stance and evaluates their potential as diagnostic, prognostic, and p redictive biomarkers in head and neck squamous cell carcinoma (HNSCC) , pancreatic ductal adenocarcinoma (PDAC), and non-small cell lung ca ncer (NSCLC). Chapter 2 reviews the current knowledge of miRNAs in HN SCC, focusing on their roles in tumorigenesis and therapeutic potenti al. Chapter 3 reports novel findings on the oncogenic role of miR-96- 5p in HNSCC and its contribution to resistance to chemotherapy and ra diotherapy. Chapter 4 reviews recent advances and challenges in the u se of EVs as biomarker and therapeutic delivery systems. Chapter 5 re ports novel findings on plasma-derived EV miR-200 family members and evaluates their diagnostic potential in PDAC. Chapter 6 focuses on mi croRNAs implicated in resistance to gemcitabine and FOLFIRINOX in pan creatic ductal adenocarcinoma (PDAC) and examines miRNA-based therape utic approaches. Chapter 7 investigates the therapeutic potential of combining tivantinib, a c-MET inhibitor, with gemcitabine in PDAC. Ch apter 8 reviews emerging treatment strategies for small cell lung can cer that extend beyond immunotherapy. Chapter 9 examines the mechanis ms underlying resistance to the nucleoside analog RX-3117 in lung can cer and proposes approaches to improve its therapeutic efficacy.
< p>More information on the thesis DESCRIPTION: The limited availability of effective treatments and the generally poor prognosis associated with many cancer types highlight the pressing need for novel therapeutic approaches and new directions in chemoresistance research. Accordingly, this thesis aims to elucid ate the mechanisms driving the development of chemoresistance and to identify potential vulnerabilities that may be exploited to improve t he effectiveness of chemotherapy. Specifically, this work examines th e role of microRNAs (miRNAs) in therapy resistance and evaluates thei r potential as diagnostic, prognostic, and predictive biomarkers in h ead and neck squamous cell carcinoma (HNSCC), pancreatic ductal adeno carcinoma (PDAC), and non-small cell lung cancer (NSCLC). Chapter 2 r eviews the current knowledge of miRNAs in HNSCC, focusing on their ro les in tumorigenesis and therapeutic potential. Chapter 3 reports nov el findings on the oncogenic role of miR-96-5p in HNSCC and its contr ibution to resistance to chemotherapy and radiotherapy. Chapter 4 rev iews recent advances and challenges in the use of EVs as biomarker an d therapeutic delivery systems. Chapter 5 reports novel findings on p lasma-derived EV miR-200 family members and evaluates their diagnosti c potential in PDAC. Chapter 6 focuses on microRNAs implicated in res istance to gemcitabine and FOLFIRINOX in pancreatic ductal adenocarci noma (PDAC) and examines miRNA-based therapeutic approaches. Chapter 7 investigates the therapeutic potential of combining tivantinib, a c -MET inhibitor, with gemcitabine in PDAC. Chapter 8 reviews emerging treatment strategies for small cell lung cancer that extend beyond im munotherapy. Chapter 9 examines the mechanisms underlying resistance to the nucleoside analog RX-3117 in lung cancer and proposes approach es to improve its therapeutic efficacy. More information on the t hesis Exploiting microRNAs as circulating biomarkers and regulato rs of key targetable proteinsto combat cancer chemoresistance END:VEVENT END:VCALENDAR