Elisa Giovannetti

VU University Medical Center and AIRC Start-Up Unit, University of Pisa

Evaluation of: Lubezky N, Loewenstein S, Ben-Haim M et al. MicroRNA expression signatures in intraductal papillary mucinous neoplasm of the pancreas. Surgery doi:10.1016/j.surg.2012.11.016 (2013) (Epub ahead of print). Pancreatic cysts are now being detected more frequently owing to increased recognition and the liberal use of cross-sectional imagi...

Toll-like receptors (TLRs), which serve as a bridge between innate and adaptive immunity, may be viable treatment targets. TLRs are the first line of defense against microbes and activate signaling cascades that induce immune and inflammatory responses. Patients with “hot” versus “cold” tumors may respond more favorably to immune checkpoint inhibit...

Background and objective: Non-small cell lung cancer (NSCLC) with Kirsten rat sarcoma viral oncogene homolog (KRAS) driver alterations harbors a poor prognosis with standard therapies, including chemotherapy and/or immunotherapy with anti-programmed cell death protein 1 (anti-PD-1) or anti-programmed death ligand-1 (anti-PD-L1) antibodies. Selecti...

Introduction: PDAC is an extremely aggressive tumor with a poor prognosis and remarkable therapeutic resistance. The dense extracellular matrix (ECM) which characterizes PDAC progression is considered a fundamental determinant of chemoresistance, with major contributions from mechanical factors. This study combined biomechanical and pharmacologica...

Background: Novel blood-based protein biomarkers may be of value for efficient, accurate, and non-invasive diagnosis of pancreatic cancer. This study assesses the diagnostic accuracy of newly recognized blood-based protein biomarkers for detecting pancreatic cancer, and investigates their added value to CA19-9, the common blood-based biomarker in c...

Supplementary data for "Diagnostic accuracy and added value of blood-based protein biomarkers for pancreatic cancer: A meta-analysis of aggregate and individual participant data." Full article: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00476-X/fulltext

Despite progress in genomic characterization, no single prognostic marker that can be evaluated using an easy-to-perform and relatively inexpensive method is available for pancreatic ductal adenocarcinoma (PDAC). MicroRNAs, which are stable, tumor- and tissue-specific molecules, are potentially ideal biomarkers, and we established an inter-laborato...

Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anti-cancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces over-expression of this protein and development of drug resistance. We thus pursued an alternative strategy that led us to the discovery of TS-dimer destabilize...

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a very poor prognosis. Therefore, there has been a focus on the identification of new biomarkers for the early diagnosis of PDAC and prediction of patient survival. Genome-wide RNA and microRNA sequencing were used using bioinformatics and Machine Learning approaches to identify...

In recent years, hyperthermia (HT) is gaining popularity as a therapeutic modality that could potentiate other treatments such as chemotherapy. Although pre-clinical and clinical research do suggest a beneficial effect of moderate HT (41.5°C), more knowledge on the molecular mechanisms is required before it can be routinely implemented in the clini...

c-Met receptor tyrosine kinase has recently emerged as an important target with therapeutic implications in pancreatic cancer. In this study, we carried out a docking virtual screening on an in-house library of 441 synthesized compounds and selected the compounds with the best interactions with the c-Met protein to be subjected to experimental test...

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood...

Pancreatic ductal adenocarcinoma (PDAC) has one of the highest incidence/death ratios among all neoplasms due to its late diagnosis and dominant chemoresistance. Most PDAC patients present with an advanced disease characterized by a multifactorial, inherent and acquired resistance to current anticancer treatments. This remarkable chemoresistance ha...

The energy metabolism of tumor cells is considered one of the hallmarks of cancer because it is different from normal cells and mainly consists of aerobic glycolysis, fatty acid oxidation, and glutaminolysis. It is about one hundred years ago since Warburg observed that cancer cells prefer aerobic glycolysis even in normoxic conditions, favoring th...

Cachexia is a metabolic syndrome consisting of massive loss of muscle mass and function that has a severe impact on the quality of life and survival of cancer patients. Up to 20% of lung cancer patients and up to 80% of pancreatic cancer patients are diagnosed with cachexia, leading to death in 20% of them. The main drivers of cachexia are cytokine...

Whereas mortality rates improved for breast and prostate cancer as a result of successful tumour biology-based therapies and biomarkers, mortality rates for pancreatic cancer patients remained stable [...]

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with rising incidence and poor prognosis. The lack of reliable prognostic biomarkers hampers the individual evaluation of the survival and recurrence potential. Methods: Here, we investigate the value of plasma levels of two potential key players in molecular mechan...

Considering the dismal survival rate, novel therapeutic strategies are warranted to improve the outcome of pancreatic ductal adenocarcinoma (PDAC). Combining nanotechnology for delivery of chemotherapeutics—preferably radiosensitizing agents—is a promising approach to enhance the therapeutic efficacy of chemoradiation. We assessed the effect of bio...

Background Colorectal-cancer (CRC) is amongst the most lethal-cancers, mainly due to its metastatic spread and drug chemoresistance. Hence there is a need for new approaches to either increase the efficacy of current therapy or introduce new therapies that have greater efficacy. There is increasing evidence that dysregulation of WNT-signaling-pathw...

Pancreatic ductal adenocarcinoma (PDAC) has one of the worst prognoses among all malignancies. PI3K/AKT/mTOR signaling pathway, a main downstream effector of KRAS is involved in the regulation of key hallmarks of cancer. We here report that whole-genome analyses demonstrate the frequent involvement of aberrant activations of PI3K/AKT/mTOR pathway c...

Objective Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with limited therapeutic options. However, metabolic adaptation to the harsh PDAC environment can expose liabilities useful for therapy. Targeting the key metabolic regulator mechanistic target of rapamycin complex 1 (mTORC1) and its downstream pathway shows efficacy only in...

Introduction: Malignant mesothelioma (MMe) is an aggressive rare cancer of the mesothelium, associated with asbestos exposure. MMe is currently an incurable disease at all stages mainly due to resistance to treatments. It is therefore necessary to elucidate key mechanisms underlying chemoresistance, in an effort to exploit them as novel therapeuti...

Monoacylglycerol lipase (MAGL) is the enzyme responsible for the metabolism of 2-arachidonoylglycerol in the brain and the hydrolysis of peripheral monoacylglycerols. Many studies demonstrated beneficial effects deriving from MAGL inhibition for neurodegenerative diseases, inflammatory pathologies, and cancer. MAGL expression is increased in invasi...

Small cell lung cancer (SCLC) arises in peribronchial locations and infiltrates the bronchial submucosa, including about 15% of lung cancer cases. Despite decades of research, the prognosis for SCLC patients remains poor because this tumor is characterized by an exceptionally high proliferative rate, strong tendency for early widespread metastasis...

Chemotherapy (CT) is the standard care for advanced pancreatic ductal adenocarcinoma (PDAC); however, with limited efficacy. Hyperthermia (HT) treatment has been suggested as a sensitizer to improve outcomes. However, the direct effect of the HT and CT combination is not fully understood. Therefore, we aim to assess the direct cytotoxic effect of H...

Mitochondria are the main energy factory in living cells. To rapidly proliferate and metastasize, neoplastic cells increase their energy requirements. Thus, mitochondria become one of the most important organelles for them. Indeed, much research shows the interplay between cancer chemoresistance and altered mitochondrial function. In this review we...

Drug resistance remains a major hurdle to successful cancer treatment, being accountable for approximately 90% of cancer-related deaths. In the past years, increasing attention has been given to the role of extracellular vesicles (EVs) in the horizontal transfer of drug resistance in cancer. Indeed, many studies have described the dissemination of...

Attempts to achieve early diagnosis are crucial to improve the outcome of patients with pancreatic ductal adenocarcinoma (PDAC). Here we present a critical evaluation of a recent study unraveling the potential of circulating AXL as a novel blood marker for early detection of PDAC and differential diagnosis from chronic pancreatitis (CP).

A new sigma-2 (σ2) receptor ligand (FA4) was efficiently synthesized and evaluated for cytotoxic, proapoptotic, and antimigratory activity on pancreatic ductal adenocarcinoma (PDAC) primary cell cultures, which restrained the aggressive and chemoresistant behavior of PDAC. This compound showed relevant antiproliferative activity with half maximal i...

Introduction: The pentose phosphate pathway (PPP) branches from glycolysis and is crucial for cell growth, since it provides necessary compounds for anabolic reactions, nucleotide synthesis and detoxification of reactive-oxygen-species (ROS). Overexpression of PPP enzymes has been reported in multiple cancer types and linked to therapy resistance,...

Pancreatic cancer (PC) is one of the most lethal malignancies. PC is characterized by a high expression of the glucose transporter GLUT-1 and of lactate dehydrogenase A (LDH-A). The novel LDH-A inhibitor NHI-Glc-2 was designed for a better uptake via GLUT-1 and was shown to be cytotoxic against the PC cell line PANC-1. Using RP-HPLC we investigated...

Background Overexpression of the angiotensin-II receptor and renin–angiotensin system (RAS) has been reported in several malignancies, including colorectal-cancer (CRC), indicating its potential value as a therapeutic target. Here we explored the impact of targeting the RAS using an angiotensin II receptor blocker, valsartan, alone and its combinat...

In recent years, a growing number of studies have evaluated the role of exosomes in pancreatic ductal adenocarcinoma cancer (PDAC) demonstrating their involvement in a multitude of pathways, including the induction of chemoresistance. The aim of this review is to present an overview of the current knowledge on the role of exosomes in the resistance...

Distinction of pancreatic ductal adenocarcinoma (PDAC) in the head of the pancreas, distal cholangiocarcinoma (dCCA), and benign periampullary conditions, is complex as they often share similar clinical symptoms. However, these diseases require specific management strategies, urging improvement of non-invasive tools for accurate diagnosis. Recent e...

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies with a 5-year survival rate of only 9%. Despite the fact that changes in glycosylation patterns during tumour progression have been reported, no systematic approach has been conducted to evaluate its potential for patient stratification. By analysing publicly av...

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal form of cancer characterized by drug resistance, urging new therapeutic strategies. In recent years, protein kinases have emerged as promising pharmacological targets for the treatment of several solid and hematological tumors. Interestingly, cyclin-dependent kinase 1 (CDK1) is overexpresse...

Background Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, with minimal therapeutic options. Aberrant tyrosine kinase activity influences tumor growth and is regulated by phosphorylation. We investigated phosphorylated kinases as target in PDAC. Methods Mass spectrometry-based phosphotyrosine proteomic analysis on PDAC cell lines...

Background and aims Acinar to Ductal Metaplasia (ADM) is the prerequisite for the initiation of Kras-driven pancreatic adenocarcinoma (PDAC) and candidate genes regulating this process are emerging from GWAS studies. The adaptor protein p130Cas emerged as a potential PDAC susceptibility gene and a Kras-synthetic lethal interactor in pancreatic cell...

Purpose of review Cancer vaccines are one of the most extensively studied immunotherapy type in solid tumors. Despite favorable presuppositions, so far, the use of cancer vaccines has been associated with disappointing results. However, a new generation of vaccines has been developed, promising to revolutionize the immunotherapy field. Recent find...

Aim: Because mutations of splicing factor 3B subunit-1 (SF3B1) have been identified in 4% of pancreatic ductal adenocarcinoma (PDAC) patients, we investigated the activity of new potential inhibitors of SF3B1 in combination with gemcitabine, one of the standard drugs, in PDAC cell lines. Methods: One imidazo[2,1-b][1,3,4]thiadiazole derivative (IS1...

The role of CDK1 in PDAC onset and development is two-fold. Firstly, since CDK1 activity regulates the G2/M cell cycle checkpoint, overexpression of CDK1 can lead to progression into mitosis even in cells with DNA damage, a potentially tumorigenic process. Secondly, CDK1 overexpression leads to the stimulation of a range of proteins that induce ste...

Pancreatic cancer is an aggressive malignancy with increasing incidence and poor prognosis due to its late diagnosis and intrinsic chemoresistance. Most pancreatic cancer patients present with locally advanced or metastatic disease characterized by inherent resistance to chemotherapy. These features pose a series of therapeutic challenges and new t...

Three generations of epidermal growth factor receptor - tyrosine kinase inhibitors (EGFR-TKIs) have been developed for treating advanced/metastatic non-small cell lung cancer (NSCLC) patients harboring EGFR-activating mutations, while a fourth generation is undergoing preclinical assessment. Although initially effective, acquired resistance to EGFR...

Background: Resistance to EGFR-TKIs constitutes a major challenge for the management of EGFR-mutated NSCLC, and recent evidence suggests that deregulation of specific microRNAs (miRNAs) may influence resistance to targeted agents. In this retrospective study, we explored the role of specific plasmatic miRNAs (miR-21, miR-27a and miR-181a) as a sur...

Background: The therapeutic potency of Rigosertib (RGS) in the treatment of the myelodysplastic syndrome has been investigated previously, but little is known about its mechanisms of action. Methods: The present study integrates systems and molecular biology approaches to investigate the mechanisms of the anti-tumor effects of RGS, either alone...

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because of diagnosis at late stage and inherent/acquired chemoresistance. Recent advances in genomic profiling and biology of this disease have not yet been translated to a relevant improvement in terms of disease management and patient’s survival. However, new possibilities...

Introduction: Recent studies suggested that extracellular vesicles (EVs) play a role both in the metastatic niche formation and in the progression of several tumors, including pancreatic cancer. In particular, the effects of EVs on metastasis should be studied in model systems that take into account both the tumor cells and the metastatic site/tum...

[This corrects the article DOI: 10.18632/oncoscience.519.].

p>Drugs that target human thymidylate synthase (hTS) are widely used in anti-cancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces its over-expression and the development of drug resistance. We thus pursued an alternative strategy that led to the discovery of TS-dimer disrupters that bind at the monomer-mon...

Drugs that target human thymidylate synthase (hTS) are widely used in anti-cancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces its over-expression and the development of drug resistance. We thus pursued an alternative strategy that led to the discovery of TS-dimer disrupters that bind at the monomer-monom...

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a notably poor prognosis, in urgent need of improved treatment strategies. The desmoplastic PDAC tumor microenvironment (TME), marked by a high concentration of cancer-associated-fibroblasts (CAFs), is a dynamic part of PDAC pathophysiology which occasions a variety of effects th...

Changes in glycosylation during tumour progression are a key hallmark of cancer. One of the glycan moieties generally overexpressed in cancer are sialic acids, which can induce immunomodulatory properties via binding to Siglec receptors. We here show that Pancreatic Ductal Adenocarcinoma (PDAC) tumour cells present an increased sialylation that can...

Introduction: Advancements in cancer management and treatment are associated with strong preclinical research data, in which reliable cancer models are demanded. Indeed, inconsistent preclinical findings and stringent regulations following the 3Rs principle of reduction, refinement, and replacement of conventional animal models currently pose chall...

MET receptor has emerged as a druggable target across several human cancers. Agents targeting MET and its ligand hepatocyte growth factor (HGF) including small molecules such as crizotinib, tivantinib and cabozantinib or antibodies including rilotumumab and onartuzumab have proven their values in different tumors. Recently, capmatinib was approved...

An interesting enzyme of the endocannabinoid system is monoacylglycerol lipase (MAGL). This enzyme, which metabolizes the endocannabinoid 2-arachidonoylglycerol (2-AG), has attracted great interest due to its involvement in several physiological and pathological processes, such as cancer progression. Experimental evidences highlighted some drawback...