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Article: Integration of liposomal irinotecan in the first-line treatment of metastatic pancreatic cancer: try to do not think about the white bear.

Melisi, Davide / Casalino, Simona / Pietrobono, Silvia / Quinzii, Alberto / Zecchetto, Camilla / Merz, Valeria

Therapeutic advances in medical oncology

2024 Volume 16, Page(s) 17588359241234487

Abstract: The approval of novel therapeutic agents remains widely reliant on evidence derived from large phase III randomized controlled trials. Liposomal irinotecan ( ... ...

Abstract	The approval of novel therapeutic agents remains widely reliant on evidence derived from large phase III randomized controlled trials. Liposomal irinotecan (ONIVYDE
Language	English
Publishing date	2024-04-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2503443-1
ISSN	1758-8359 ; 1758-8340
ISSN (online)	1758-8359
ISSN	1758-8340
DOI	10.1177/17588359241234487
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Article ; Online: Pemigatinib, a potent inhibitor of FGFRs for the treatment of cholangiocarcinoma.

Merz, Valeria / Zecchetto, Camilla / Melisi, Davide

Future oncology (London, England)

2020 Volume 17, Issue 4, Page(s) 389–402

Abstract: The prognosis of patients affected by cholangiocarcinoma is classically poor. Until recently, chemotherapeutic drugs were the only systemic treatment option available, leading to an overall survival lower than 1 year. In recent decades, different genetic ...

Abstract	The prognosis of patients affected by cholangiocarcinoma is classically poor. Until recently, chemotherapeutic drugs were the only systemic treatment option available, leading to an overall survival lower than 1 year. In recent decades, different genetic alterations have been identified as playing a key role in the oncogenic signaling. A subgroup of intrahepatic cholangiocarcinoma is characterized by
MeSH term(s)	Bile Duct Neoplasms/drug therapy ; Cholangiocarcinoma/drug therapy ; Drug Resistance, Neoplasm ; Humans ; Morpholines/adverse effects ; Morpholines/therapeutic use ; Pyrimidines/adverse effects ; Pyrimidines/therapeutic use ; Pyrroles/adverse effects ; Pyrroles/therapeutic use ; Receptors, Fibroblast Growth Factor/antagonists & inhibitors
Chemical Substances	Morpholines ; Pyrimidines ; Pyrroles ; Receptors, Fibroblast Growth Factor ; pemigatinib (Y6BX7BL23K)
Language	English
Publishing date	2020-10-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2274956-1
ISSN	1744-8301 ; 1479-6694
ISSN (online)	1744-8301
ISSN	1479-6694
DOI	10.2217/fon-2020-0726
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Zs.A 6478: Show issues

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Article: Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma: Role of the Radiologist and Oncologist in the Era of Precision Medicine.

Vernuccio, Federica / Messina, Carlo / Merz, Valeria / Cannella, Roberto / Midiri, Massimo

Diagnostics (Basel, Switzerland)

2021 Volume 11, Issue 11

Abstract: The incidence and mortality of pancreatic ductal adenocarcinoma are growing over time. The management of patients with pancreatic ductal adenocarcinoma involves a multidisciplinary team, ideally involving experts from surgery, diagnostic imaging, ... ...

Abstract	The incidence and mortality of pancreatic ductal adenocarcinoma are growing over time. The management of patients with pancreatic ductal adenocarcinoma involves a multidisciplinary team, ideally involving experts from surgery, diagnostic imaging, interventional endoscopy, medical oncology, radiation oncology, pathology, geriatric medicine, and palliative care. An adequate staging of pancreatic ductal adenocarcinoma and re-assessment of the tumor after neoadjuvant therapy allows the multidisciplinary team to choose the most appropriate treatment for the patient. This review article discusses advancement in the molecular basis of pancreatic ductal adenocarcinoma, diagnostic tools available for staging and tumor response assessment, and management of resectable or borderline resectable pancreatic cancer.
Language	English
Publishing date	2021-11-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics11112166
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Article ; Online: Efficacy and safety of PD1/PDL1 blockade with platinum-based chemotherapy for extensive small cell lung cancer: A pooled analysis of randomized trials.

Messina, Carlo / Salati, Massimiliano / Messina, Marco / Cattrini, Carlo / Merz, Valeria / Caffo, Orazio

European journal of clinical investigation

2021 Volume 51, Issue 5, Page(s) e13483

MeSH term(s)	Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Etoposide/administration & dosage ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology ; Platinum Compounds/administration & dosage ; Randomized Controlled Trials as Topic ; Small Cell Lung Carcinoma/drug therapy ; Small Cell Lung Carcinoma/pathology
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Immune Checkpoint Inhibitors ; Platinum Compounds ; durvalumab (28X28X9OKV) ; atezolizumab (52CMI0WC3Y) ; Etoposide (6PLQ3CP4P3) ; pembrolizumab (DPT0O3T46P)
Language	English
Publishing date	2021-01-17
Publishing country	England
Document type	Letter ; Meta-Analysis
ZDB-ID	186196-7
ISSN	1365-2362 ; 0014-2972 ; 0960-135X
ISSN (online)	1365-2362
ISSN	0014-2972 ; 0960-135X
DOI	10.1111/eci.13483
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Zs.A 677: Show issues

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Article: Targeting FGFR Pathway Is Not an Effective Therapeutic Strategy in Patients with Unselected Metastatic Esophagogastric Cancer Resistant to Trastuzumab.

Zecchetto, Camilla / Quinzii, Alberto / Casalino, Simona / Gaule, Marina / Pesoni, Camilla / Merz, Valeria / Pietrobono, Silvia / Mangiameli, Domenico / Pasquato, Martina / Milleri, Stefano / Giacopuzzi, Simone / Bencivenga, Maria / Tomezzoli, Anna / de Manzoni, Giovanni / Melisi, Davide

Journal of personalized medicine

2023 Volume 13, Issue 3

Abstract: Trastuzumab plus chemotherapy is the standard of care for the first-line treatment of patients with HER2+ advanced esophagogastric (EG) cancer. Nevertheless, patients frequently develop resistance. In preclinical models, we identified the overexpression ... ...

Abstract	Trastuzumab plus chemotherapy is the standard of care for the first-line treatment of patients with HER2+ advanced esophagogastric (EG) cancer. Nevertheless, patients frequently develop resistance. In preclinical models, we identified the overexpression of Fibroblast Growth Factor Receptor (FGFR) 3 as a mechanism potentially involved in trastuzumab-acquired resistance. FGFR inhibition could be a potential mechanism as a second-line treatment. In this Simon's two-stage phase 2, single arm study, patients with advanced EG cancer refractory to trastuzumab-containing therapies received pemigatinib, an inhibitor of FGFR. The primary end point was the 12-week progression-free survival rate. Translational analyses were performed on tissue and plasma samples. Eight patients were enrolled in the first stage. Although the 6-week disease control rate was 25%, only one patient achieved a stable disease after 12 weeks of treatment. The trial was discontinued before the second stage. Two out of six evaluable tumor samples expressed FGFR3. No
Language	English
Publishing date	2023-03-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm13030508
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Article ; Online: Electronic Medical Record-Assisted Telephone Follow-Up of Breast Cancer Survivors During the COVID-19 Pandemic: A Single Institution Experience.

Merz, Valeria / Ferro, Antonella / Piras, Enrico Maria / Zanutto, Alberto / Caffo, Orazio / Messina, Carlo

JCO oncology practice

2020 Volume 17, Issue 1, Page(s) e44–e52

Abstract: Purpose: The COVID-19 outbreak rapidly became a public health emergency and led to radical changes in patient management. From the start of the pandemic, we used electronic medical record-assisted telephone follow-up (E-TFU) of cancer survivors (CS) to ... ...

Abstract	Purpose: The COVID-19 outbreak rapidly became a public health emergency and led to radical changes in patient management. From the start of the pandemic, we used electronic medical record-assisted telephone follow-up (E-TFU) of cancer survivors (CS) to minimize hospital exposure. The aim of this prospective study was to assess how breast cancer survivors (bCSs) perceived E-TFU. Materials and methods: A 15-item survey was e-mailed to bCSs who had been managed with E-TFU. The responses were measured using Likert-like scales and were correlated with the main characteristics of the bCS using Pearson's test. Results: One hundred thirty-seven of 343 bCSs (40%) completed the survey between March 9 and June 2, 2020. Their median age was 59 years. Although 80.3% of bCSs were satisfied with E-TFU, only 43.8% would like to have E-TFU in the future. A low educational level was correlated with higher COVID-19-related anxiety ( Conclusion: E-TFU was an important means of avoiding hospital contacts during the COVID-19 pandemic, and the majority of bCSs in the survey were satisfied with this procedure. Further studies are needed to investigate the implementation of telemedicine even outside an emergency situation.
MeSH term(s)	Adult ; Aged ; Breast Neoplasms/epidemiology ; Breast Neoplasms/pathology ; Breast Neoplasms/therapy ; COVID-19/complications ; COVID-19/epidemiology ; COVID-19/pathology ; Cancer Survivors ; Electronic Health Records ; Female ; Follow-Up Studies ; Hospitals ; Humans ; Male ; Middle Aged ; Pandemics ; Patient Discharge ; Patient Satisfaction ; SARS-CoV-2/pathogenicity ; Telemedicine ; Telephone
Language	English
Publishing date	2020-12-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	3028198-2
ISSN	2688-1535 ; 2688-1527
ISSN (online)	2688-1535
ISSN	2688-1527
DOI	10.1200/OP.20.00643
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Zs.A 7198: Show issues

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Article ; Online: Autotaxin Secretion Is a Stromal Mechanism of Adaptive Resistance to TGFβ Inhibition in Pancreatic Ductal Adenocarcinoma.

Pietrobono, Silvia / Sabbadini, Fabio / Bertolini, Monica / Mangiameli, Domenico / De Vita, Veronica / Fazzini, Federica / Lunardi, Giulia / Casalino, Simona / Scarlato, Enza / Merz, Valeria / Zecchetto, Camilla / Quinzii, Alberto / Di Conza, Giusy / Lahn, Michael / Melisi, Davide

Cancer research

2023 Volume 84, Issue 1, Page(s) 118–132

Abstract: The TGFβ receptor inhibitor galunisertib demonstrated efficacy in patients with pancreatic ductal adenocarcinoma (PDAC) in the randomized phase II H9H-MC-JBAJ study, which compared galunisertib plus the chemotherapeutic agent gemcitabine with gemcitabine ...

Abstract	The TGFβ receptor inhibitor galunisertib demonstrated efficacy in patients with pancreatic ductal adenocarcinoma (PDAC) in the randomized phase II H9H-MC-JBAJ study, which compared galunisertib plus the chemotherapeutic agent gemcitabine with gemcitabine alone. However, additional stromal paracrine signals might confer adaptive resistance that limits the efficacy of this therapeutic strategy. Here, we found that autotaxin, a secreted enzyme that promotes inflammation and fibrosis by generating lysophosphatidic acid (LPA), mediates adaptive resistance to TGFβ receptor inhibition. Blocking TGFβ signaling prompted the skewing of cancer-associated fibroblasts (CAF) toward an inflammatory (iCAF) phenotype. iCAFs were responsible for a significant secretion of autotaxin. Paracrine autotaxin increased LPA-NFκB signaling in tumor cells that triggered treatment resistance. The autotaxin inhibitor IOA-289 suppressed NFκB activation in PDAC cells and overcame resistance to galunisertib and gemcitabine. In immunocompetent orthotopic murine models, IOA-289 synergized with galunisertib in restoring sensitivity to gemcitabine. Most importantly, treatment with galunisertib significantly increased plasma levels of autotaxin in patients enrolled in the H9H-MC-JBAJ study, and median progression-free survival was significantly longer in patients without an increase of autotaxin upon treatment with galunisertib compared with those with increased autotaxin. These results establish that autotaxin secretion by CAFs is increased by TGFβ inhibition and that circulating autotaxin levels predict response to the combination treatment approach of gemcitabine plus galunisertib. Significance: TGFβ inhibition skews cancer-associated fibroblasts toward an inflammatory phenotype that secretes autotaxin to drive adaptive resistance in PDAC, revealing autotaxin as a therapeutic target and biomarker of galunisertib response.
MeSH term(s)	Humans ; Animals ; Mice ; Gemcitabine ; Transforming Growth Factor beta ; Carcinoma, Pancreatic Ductal/pathology ; Pancreatic Neoplasms/pathology ; Signal Transduction
Chemical Substances	Gemcitabine ; Transforming Growth Factor beta
Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Clinical Trial, Phase II ; Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-23-0104
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Article: YAP Activation Is Associated with a Worse Prognosis of Poorly Cohesive Gastric Cancer.

Bencivenga, Maria / Torroni, Lorena / Dal Cero, Mariagiulia / Quinzii, Alberto / Zecchetto, Camilla / Merz, Valeria / Casalino, Simona / Taus, Francesco / Pietrobono, Silvia / Mangiameli, Domenico / Filippini, Federica / Alloggio, Mariella / Castelli, Claudia / Iglesias, Mar / Pera, Manuel / Melisi, Davide

Journal of personalized medicine

2023 Volume 13, Issue 9

Abstract: Poorly cohesive (PC) gastric cancer (GC) is extremely aggressive in progression, and there is an urgent need to identify the molecular pathways involved. We hypothesized the essential role of the RhoA-YAP axis in these mechanisms. The present ... ...

Abstract	Poorly cohesive (PC) gastric cancer (GC) is extremely aggressive in progression, and there is an urgent need to identify the molecular pathways involved. We hypothesized the essential role of the RhoA-YAP axis in these mechanisms. The present observational multicenter retrospective study included 133 patients with PC GC treated at two dedicated European surgical centers between 2004 and 2014. YAP nuclear localization was measured by immunohistochemical (IHC) analysis of tissue biopsies. The complete absence of nuclear reactivity was coded as negative expression; we considered "any positive" as low nuclear expression (>0% but <10% of cells) and high nuclear expression (≥10% of cells). Women represented about half of the present series (52%), and the median age was 64 years (p25-p75 range: 53-75). Neoadjuvant and adjuvant treatments were administered to 10% and 54% of the cases, respectively. Extended systemic lymphadenectomy (D2) was the most common (54%). In nearly all cases, the number of retrieved nodes was ≥15, i.e., adequate for tumor staging (94%). An R0 resection was achieved in 80% of the cases. Most patients were pathological T stage 3 and 4 (pT3/pT4 = 79.0%) and pathological N stage 2, 3a, and 3b (pN2/pN3a/pN3b = 47.0%) at the pathological examination. Twenty patients (15%) presented distant metastases. Five-year overall survival (OS) was significantly higher (
Language	English
Publishing date	2023-08-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm13091294
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Article ; Online: Exceptional Clinical Response to Alectinib in Pancreatic Acinar Cell Carcinoma With a Novel ALK-KANK4 Gene Fusion.

Gaule, Marina / Pesoni, Camilla / Quinzii, Alberto / Zecchetto, Camilla / Casalino, Simona / Merz, Valeria / Contarelli, Serena / Pietrobono, Silvia / Vissio, Elena / Molinaro, Luca / Manzin, Enrica / Volpatto, Roberta / Vellani, Giorgio / Melisi, Davide

JCO precision oncology

2022 Volume 6, Page(s) e2100400

MeSH term(s)	Anaplastic Lymphoma Kinase/genetics ; Ankyrin Repeat/genetics ; Carbazoles/therapeutic use ; Carcinoma, Acinar Cell/drug therapy ; Carcinoma, Acinar Cell/genetics ; Gene Fusion ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Piperidines/therapeutic use ; Treatment Outcome
Chemical Substances	Carbazoles ; Piperidines ; ALK protein, human (EC 2.7.10.1) ; Anaplastic Lymphoma Kinase (EC 2.7.10.1) ; alectinib (LIJ4CT1Z3Y)
Language	English
Publishing date	2022-01-10
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2473-4284
ISSN (online)	2473-4284
DOI	10.1200/PO.21.00400
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Article: Predictive Biomarkers for a Personalized Approach in Resectable Pancreatic Cancer.

Merz, Valeria / Mangiameli, Domenico / Zecchetto, Camilla / Quinzii, Alberto / Pietrobono, Silvia / Messina, Carlo / Casalino, Simona / Gaule, Marina / Pesoni, Camilla / Vitale, Pasquale / Trentin, Chiara / Frisinghelli, Michela / Caffo, Orazio / Melisi, Davide

Frontiers in surgery

2022 Volume 9, Page(s) 866173

Abstract: The mainstay treatment for patients with immediate resectable pancreatic cancer remains upfront surgery, which represents the only potentially curative strategy. Nevertheless, the majority of patients surgically resected for pancreatic cancer experiences ...

Abstract	The mainstay treatment for patients with immediate resectable pancreatic cancer remains upfront surgery, which represents the only potentially curative strategy. Nevertheless, the majority of patients surgically resected for pancreatic cancer experiences disease relapse, even when a combination adjuvant therapy is offered. Therefore, aiming at improving disease free survival and overall survival of these patients, there is an increasing interest in evaluating the activity and efficacy of neoadjuvant and perioperative treatments. In this view, it is of utmost importance to find biomarkers able to select patients who may benefit from a preoperative therapy rather than upfront surgical resection. Defined genomic alterations and a dynamic inflammatory microenvironment are the major culprits for disease recurrence and resistance to chemotherapeutic treatments in pancreatic cancer patients. Signal transduction pathways or tumor immune microenvironment could predict early recurrence and response to chemotherapy. In the last decade, distinct molecular subtypes of pancreatic cancer have been described, laying the bases to a tailored therapeutic approach, started firstly in the treatment of advanced disease. Patients with homologous repair deficiency, in particular with mutant germline BRCA genes, represent the first subgroup demonstrating to benefit from specific therapies. A fraction of patients with pancreatic cancer could take advantage of genome sequencing with the aim of identifying possible targetable mutations. These genomic driven strategies could be even more relevant in a potentially curative setting. In this review, we outline putative predictive markers that could help in the next future in tailoring the best therapeutic strategy for pancreatic cancer patients with a potentially curable disease.
Language	English
Publishing date	2022-05-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2773823-1
ISSN	2296-875X
ISSN	2296-875X
DOI	10.3389/fsurg.2022.866173
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