Search results for "epiderma"
showing 10 items of 296 documents
The significance of epidermal growth factor receptor uncommon mutations in non-small cell lung cancer: A systematic review and critical appraisal
2020
Uncommon epidermal growth factor receptor (EGFR) mutations collectively account for 10% of EGFR mutations, harboring heterogeneous molecular alterations within exons 18-21 with clinically variable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced Non-Small Cell Lung Cancer (NSCLC) patients. In addition, with the introduction of different NGS gene approach an improvement of EGFR mutations detection was reported. Today, no specific studies have prospectively evaluated uncommon sensitizing mutations in detail and no firm standard of care has been established in the first-line setting. The aim of this comprehensive review is to critically consider the clinical role of uncommon EGF…
Genetic regulation and function of epidermal growth factor receptor signalling in patterning of the embryonicDrosophilabrain
2016
The specification of distinct neural cell types in central nervous system development crucially depends on positional cues conferred to neural stem cells in the neuroectoderm. Here, we investigate the regulation and function of the epidermal growth factor receptor (EGFR) signalling pathway in early development of theDrosophilabrain. We find that localized EGFR signalling in the brain neuroectoderm relies on a neuromere-specific deployment of activating (Spitz, Vein) and inhibiting (Argos) ligands. Activated EGFR controls the spatially restricted expression of all dorsoventral (DV) patterning genes in a gene- and neuromere-specific manner. Further, we reveal a novel role of DV genes—ventral …
How to Deal with Second Line Dilemma in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis
2019
Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy with chemotherapy (CT) as second line treatment for metastatic colorectal cancer (mCRC). The right sequence of the treatments in all RAS (KRAS/NRAS) wild type (wt) patients has not precisely defined. We evaluated the impact of aforementioned targeted therapies in second line setting, analyzing efficacy and safety data from phase III clinical trials. We performed both direct and indirect comparisons between anti-EGFR and anti-VEGF. Outcomes included disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall su…
Immune checkpoint inhibitors in lung cancer: the holy grail has not yet been found…
2017
Lung cancer is rich in molecular complexities and driven by different abnormal molecular pathways. Personalised medicine has begun to bring new hope for the treatment of patients with lung cancer, especially non-small cell lung cancer (NSCLC). The development of molecularly targeted therapy (small molecules and monoclonal antibodies) has significantly improved outcomes in the metastatic setting for patients with NSCLC whose tumours harbour activated oncogenes such as epidermal growth factor receptor (EGFR) and translocated genes like anaplastic lymphoma kinase (ALK). In addition, immune checkpoint inhibitors have also dramatically changed the therapeutic landscape of NSCLC. In particular, m…
The prognostic relevance of HER2-positivity gain in metastatic breast cancer in the ChangeHER trial
2021
Breast cancer (BC) heterogeneity is composite in nature, with a wide variety of factors concurring to define several pathological entities, which differ by clinical presentation, pathologic features, therapy administered, and inherent outcomes1. Additional sources of breast cancer heterogeneity may raise during the disease course. In BC patients whose disease was initially diagnosed in the early stage and subsequently progressed with metastatic involvement of one single or multiple site/s, the molecular characteristics of metastatic lesions do not necessary mimic those of the disease initially diagnosed. A well-depicted molecular landscape is crucial for subtype definition, prognostic evalu…
EGFR inhibition in NSCLC: New findings…. and opened questions?
2017
The 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 f…
Comprehensive cross-platform comparison of methods for non-invasive EGFR mutation testing : results of the RING observational trial
2020
Plasma samples from 72 EGFR‐mutant advanced NSCLC patients, collected upon progression to first‐line TKI, were analyzed by seven methodologies (two NGS‐based methods, three high‐sensitivity PCR‐based platforms, and two FDA‐approved methods). Our study demonstrates a good to excellent agreement between methodologies and supports the use of liquid biopsies for therapy decision‐making.
Phase Ib study evaluating safety and clinical activity of the anti-HER3 antibody lumretuzumab combined with the anti-HER2 antibody pertuzumab and pac…
2018
Summary Purpose To investigate the safety and clinical activity of comprehensive human epidermal growth factor receptor (HER) family receptor inhibition using lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2-low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors. Patients received lumretuzumab (1000 mg in Cohort 1; 500 mg in Cohorts 2 and 3) plus pertuzumab (840 mg loading dose [LD] followed by 420 mg in Cohorts 1 and 2; 420 mg without LD in Cohort 3) every 3 weeks, plus paclitaxel (8…
Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives
2017
Carcinosarcomas (CS) in gynecology are very infrequent and represent only 2–5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% and recurrence is extremely common (50–80%). Due to the poor prognosis of CS, new strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. In this paper, we aimed to gather the available evidence on the latest therapies for the treatment of CS. We performed a systematic review using the terms “uterine carcinosarcoma”, “uterine Malignant Mixed Müllerian Tumors”, “target therapies”,…
Nintedanib in NSCLC: evidence to date and place in therapy
2016
The treatment of advanced non-small cell lung cancer (NSCLC) is currently driven by the detection of targetable oncogenic drivers, i.e. epidermal growth factor receptor, echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase, etc. Those patients who are wildtype for known and valuable oncogenes can receive standard chemotherapy as first-line treatment, with the possibility of adding bevacizumab. With regard to second-line treatment, nintedanib can improve the efficacy of docetaxel. Nintedanib is a tyrosine kinase inhibitor targeting three angiogenesis-related transmembrane receptors. The usefulness of nintedanib as an anticancer agent for NSCLC has been proved by both …