Anastasios Gkountakos

• University of Verona

Background BReast CAncer gene 1 (BRCA1) and BReast CAncer gene 2 (BRCA2) encode for tumor suppressor proteins which are critical regulators of the Homologous Recombination (HR) pathway, the most precise and important DNA damage response mechanism. Dysfunctional HR proteins cannot repair double-stranded DNA breaks in mammalian cells, a situation cal...

BReast CAncer gene 1 (BRCA1) and BReast CAncer gene 2 (BRCA2) encode for tumor suppressor proteins which are critical regulators of the homologous recombination (HR) pathway, the most precise and important DNA damage response mechanism. Dysfunctional HR proteins cannot repair double-stranded DNA breaks in mammalian cells, a situation called HR defi...

Pulmonary large cell carcinoma (LCC) is an undifferentiated neoplasm lacking morphological, histochemical, and immunohistochemical features of small cell lung cancer, adenocarcinoma (ADC), or squamous cell carcinoma (SCC). The available molecular information on this rare disease is limited. This study aimed to provide an integrated molecular overvi...

Neuroendocrine neoplasms (NENs) are a heterogeneous group of diseases that are characterized by different behavior and clinical manifestations. The diagnosis and management of this group of tumors are challenging due to tumor complexity and lack of precise and widely validated biomarkers. Indeed, the current circulating mono-analyte biomarkers (suc...

Background: Intestinal neuroendocrine tumours (I-NETs) represent a non-negligible entity among intestinal neoplasms, with metastatic spreading usually present at the time of diagnosis. In this context, effective molecular actionable targets are still lacking. Through transcriptome analysis, we aim at refining the molecular taxonomy of I-NETs, also...

Signet-ring cell/poorly cohesive cell (SRC) carcinoma is an aggressive variant of pancreatic ductal adenocarcinoma (PDAC). This study aimed to clarify its clinicopathological and molecular profiles based on a multi-institutional cohort of 20 cases. The molecular profiles were investigated using DNA and RNA sequencing. The clinicopathological parame...

Simple Summary Pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are very aggressive neoplasms. However, effective treatments are still limited. Starting from a common embryogenesis of the tissue of origin, these two cancer types share several histomolecular features, which renders a differential diagnosis challenging. Ho...

Pancreatic neuroendocrine neoplasms (PanNENs) are rare neoplasms arising from islets of the Langerhans in the pancreas. They can be divided into two groups, based on peptide hormone secretion, functioning and nonfunctioning PanNENs. The first group is characterized by different secreted peptides causing specific syndromes and is further classified...

Background: Combined large cell neuroendocrine carcinoma (CoLCNEC) is given by the association of LCNEC with adeno or squamous or any non-neuroendocrine carcinoma. Molecular bases of CoLCNEC pathogenesis are scant and no standardized therapies are defined. Methods: 44 CoLCNECs: 26 with adenocarcinoma (CoADC), 7 with squamous cell carcinoma (CoSQ...

Undifferentiated sarcomatoid carcinoma (USC) of the pancreas is a rare but especially aggressive variant of pancreatic ductal adenocarcinoma (PDAC), composed of at least 80% of sarcomatoid cells. This study aimed to elucidate its clinicopathological and molecular features. The study cohort included 10 patients with pancreatic USC. Clinicopathologic...

The use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as first-line treatment in patients with lung adenocarcinoma (LUAD) harboring EGFR-activating mutations has resulted in a dramatic improvement in the management of the disease. However, the long-term clinical benefit is inevitably compromised by multiple resistance...

Undifferentiated sarcomatoid carcinoma of the pancreas (SCP) is a rare and aggressive subtype of pancreatic cancer. Histologically, SCP is a poorly differentiated tumor characterized by the lack of glandular differentiation and the presence of mesenchymal-like, spindle-shaped tumor cells. Due to its rarity, only sporadic cases have been reported, w...

The introduction of immune checkpoint inhibitor (ICI)-based therapy for non-oncogene addicted non-small cell lung cancer (NSCLC) has significantly transformed the treatment landscape of the disease. Inhibitors of the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint axis, which were initially considered as a l...

To evaluate the nutritional status and its correlation with outcome in advanced (A) non-small cell lung cancer (NSCLC) pts. A-NSCLC pts treated at AOUI of Verona (2016-2018) received nutritional counseling by a skilled dietitian. Nutritional Risk Screening (NRS) 2002 was used to assess nutritional risk. Bilateral psoas major muscles were measured a...

Lung cancer remains the leading cause of cancer-related death worldwide. Affected patients frequently experience debilitating disease-related symptoms, including dyspnea, cough, fatigue, anxiety, depression, insomnia, and pain, despite the progresses achieved in term of treatment efficacy. Physical activity and exercise are nonpharmacological inter...

Background Weight loss and lean body mass wasting are highly prevalent in NSCLC pts, but frequently underestimated. This study aimed to assess the prevalence of malnutrition and its correlation with outcome in A-NSCLC pts. Methods A-NSCLC pts treated at AOUI of Verona (2016-2018) received nutritional counselling by a qualified dietitian. Nutrition...

Background Specific genomic abnormalities in immune-escape/editing-related genes have been demonstrated to be associated with immunotherapy resistance. In the light of this hypothesis, with the final aim to identify a potential predictive signature for immunotherapy, we designed the PRINCiPe (Predictors of Resistance to Immunotherapy with NIV) stud...

Lung cancer is the most common malignancy and cause of cancer deaths worldwide, owing to the dismal prognosis for most affected patients. Phosphatase and tensin homolog deleted in chromosome 10 (PTEN) acts as a powerful tumor suppressor gene and even partial reduction of its levels increases cancer susceptibility. While the most validated anti-onco...

Aim: With the final aim to explore the first-line treatment options for non-small-cell lung cancer (NSCLC) patients, we performed a systematic review and literature-based meta-analysis of available clinical trials exploring immunotherapy in combination versus standard histology-based chemotherapy. Materials & methods: We evaluated interactions acco...

Weight loss and depletion of nutritional status are frequent presentation hallmarks in non-small cell lung cancer (NSCLC). Decline in muscle mass is a major component in weight loss and may have both a prognostic and predictive value for survival and treatment-related toxicities. Recent findings suggest that weight and skeletal muscle mass gain dur...

Genomic alterations affecting components of the mechanistic target of rapamycin (mTOR) pathway are found rather frequently in cancers, suggesting that aberrant pathway activity is implicated in oncogenesis of different tumor types. mTOR functions as the core catalytic kinase of two distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), which c...

Introduction: In non-small-cell lung cancer (NSCLC) the recent introduction of immunotherapy in daily clinical practice produced a wave of enthusiasm, however, this was rapidly moderated by the evidence that only some patients could experience a relevant clinical benefit. Therefore, a great effort from the scientific community has been dedicated to...

The MET proto-oncogene plays crucial roles in cell growth and proliferation, survival and apoptosis, epithelial-mesenchymal transition (EMT) and invasion, potentially conditioning the development and progression of the carcinogenesis process. The MET-associated aberrant signaling could be triggered by a variety of mechanisms, such as mutations, gen...

Innovative therapeutic agents have significantly improved outcomes, with an acceptable safety profile, in a substantial proportion of non-small cell lung cancer (NSCLC) patients in whom the malignant phenotype of the disease is determined by oncogenic molecular alterations. However, the benefit seen with these treatment models has not translated we...