49 research outputs found
Liquid Biopsy in Gynecological Cancers
No full textGynecological cancers originate in woman’s reproductive organs, including ovarian, uterine or endometrial, cervical, vulvar, and vaginal cancers. These tumors are a leading health problem for women accounting for more than 20% of new cases and cancer-related deaths worldwide. Gynecological cancers are characterized by an aggressive biological behavior with a clinical presentation often in advanced stage of disease. This chapter will focus on the potential role of the novel molecular approaches based on liquid biopsy in detecting occult disease, monitoring the progression and identifying treatment-resistance in gynecological cancer patients. The ability to detect circulating tumor DNA (ct-DNA), Exosome and Circulating miRNA, as novel molecular biomarkers is possible thanks to the advent of novel high throughput sequencing technologies and new analytical techniques, which favoured the spreading of the personalized medicine worldwide.
M. Castiglia and A. Listì authors contributed equally to this work
Non-coding RNAs functioning in colorectal cancer stem cells
No full textIn recent years, the hypothesis of the presence of tumor-initiating cancer stem cells (CSCs) has received a considerable support. This model suggested the existence of CSCs which, thanks to their self-renewal properties, are able to drive the expansion and the maintenance of malignant cell populations with invasive and metastatic potential in cancer. Increasing evidence showed the ability of such cells to acquire self-renewal, multipotency, angiogenic potential, immune evasion, symmetrical and asymmetrical divisions which, along with the presence of several DNA repair mechanisms, further enhance their oncogenic potential making them highly resistant to common anticancer treatments. The main signaling pathways involved in the homeostasis of colorectal (CRC) stem cells are the Wnt, Notch, Sonic Hedgehog, and Bone Morfogenic Protein (BMP) pathways, which are mostly responsible for all the features that have been widely referred to stem cells. The same pathways have been identifi ed in colorectal cancer stem cells (CRCSCs), conferring a more aggressive phenotype compared to non-stem CRC cells. Recently, several evidences suggested that non-coding RNAs (ncRNAs) may play a crucial role in the regulation of different biological mechanisms in CRC, by modulating the expression of critical stem cell transcription factors that have been found active in CSCs. In this chapter, we will discuss the involvement of ncRNAs, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in stemness acquisition and maintenance by CRCSCs, through the regulation of pathways modulating the CSC phenotype and growth, carcinogenesis, differentiation, and epithelial to mesenchymal transition (EMT)
Metastatic site location may influence the diagnostic accuracy of plasma EGFR-mutation testing in NSCLC: A pooled analysis
No full textEGFR inhibition in NSCLC: New findings.... and opened questions?
No full textThe targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients’ outcomes. In this review we summarize the most important recent findings regarding EGFR-inhibition in NSCLC, highlighting the current unsolved questions on the selection of the best TKI in first-line, which therapy can be combined with upfront EGFR-TKIs, how to overcome acquired resistance, and which are the clinical applications of liquid biopsy
Optimizing the clinical management of EGFR-mutant advanced non-small cell lung cancer: a literature review
No full textBACKGROUND AND OBJECTIVE: Despite several steps forward in the treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), however there are still pending issues and upcoming challenges requiring adequate addressing in order to optimize the clinical management of metastatic patients harboring molecular alterations within the EGFR gene. This review aims to summarize the most recent findings regarding the diagnostic testing and therapeutic strategies of EGFR-mutant advanced NSCLC. METHODS: Literature search was conducted using MEDLINE/PubMed, EMBASE, Scopus and Cochrane Library databases, up to December 2021. Relevant studies in English language published between 2004 and 2021 were selected. KEY CONTENT AND FINDINGS: The increased detection of uncommon EGFR mutations in the real-word practice along with the clinical development of novel selective inhibitors, highlighted the issue of an adequate selection of the best EGFR-tyrosine-kinase inhibitor (TKI) to the right patient mutation. The advent of osimertinib in first-line has dramatically changed the spectrum of molecular mechanisms underlying both innate and acquired resistance to the EGFR-TKI therapy, accelerating the clinical investigation of novel genomic-driven sequential strategies as well as upfront targeted combinations. The recent approval of potent, selective inhibitors targeting the EGFR exon-20 insertions, renewed interest toward this patients’ subset, questioning the diagnostic accuracy of old-standard genomic sequencing technologies and pushing the implementations of next-generation sequencing (NGS)-based molecular profiling in the real word practice scenario. CONCLUSIONS: This review provides evidence-based answers to the aforementioned challenges aiming to optimize the clinical management of metastatic patients harboring molecular alterations within the EGFR gene
Potential miRNAs involved in molecular pathways mediating the anticancer effects of short term starvation in breast cancer cells treated with doxorubicin
No full textProgrammed Death Ligand 1 (PD-L1) as a Predictive Biomarker for Pembrolizumab Therapy in Patients with Advanced Non–Small-Cell Lung Cancer (NSCLC)
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Circulating tumor DNA (ctDNA) as predictive biomarker in NSCLC patients treated with nivolumab
No full textMolecular Testing and Treatment Strategies in RET-Rearranged NSCLC Patients: Stay on Target to Look Forward
No full textRET alterations are recognized as key oncogenic drivers in different cancer types, including non-small cell lung cancer (NSCLC). Multikinase inhibitors (MKIs) with anti-RET activities resulted in variable efficacy with significant toxicities because of low target specificity. Selective RET kinase inhibitors, such as pralsetinib and selepercatinib, demonstrated high efficacy and favorable tolerability in advanced RET-rearranged NSCLC patients, leading to their introduction in the clinical setting. Among the different approaches available for the identification of RET rearrangements, next-generation sequencing (NGS) assays present substantial advantages in terms of turnaround time and diagnostic accuracy, even if potentially limited by accessibility issues. The recent advent of novel effective targeted therapies raises several questions regarding the emergence of resistance mechanisms and the potential ways to prevent/overcome them. In this review, we discuss molecular testing and treatment strategies to manage RET fusion positive NSCLC patients with a focus on resistance mechanisms and future perspectives in this rapidly evolving scenario
