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Author Silvestre Vicent

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Liver Kinase B1 (LKB1) Loss Has its p-ERKs: ERK Inactivation as a Vulnerability in NSCLC With LKB1 Mutations.

Irati Macaya, Rodrigo Entrialgo-Cadierno, Karmele Valencia, Silvestre Vicent,

J Thorac Oncol (Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer)
[2020, 15(3):311-313]

Cited: 0 times

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The Mir181ab1 cluster promotes KRAS-driven oncogenesis and progression in lung and pancreas.

Karmele Valencia, Oihane Erice, Kaja Kostyrko, Simone Hausmann, Elizabeth Guruceaga, Anuradha Tathireddy, Natasha M Flores, Leanne C Sayles, Alex G Lee, Rita Fragoso, Tian-Qiang Sun, Adrian Vallejo, Marta Roman, Rodrigo Entrialgo-Cadierno, Itziar Migueliz, Nerea Razquin, Puri Fortes, Fernando Lecanda, Jun Lu, Mariano Ponz-Sarvise, Chang-Zheng Chen, Pawel K Mazur, E Alejandro Sweet-Cordero, Silvestre Vicent,

Few therapies are currently available for patients with KRAS-driven cancers, highlighting the need to identify new molecular targets that modulate central downstream effector pathways. Here we found that the microRNA (miRNA) cluster including miR181ab1 is a key modulator of KRAS-driven oncogenesis. Ablation of Mir181ab1 in genetically engineered mouse models of ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2020, 130(4):1879-1895]

Cited: 0 times

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FGFR1 and FGFR4 oncogenicity depends on n-cadherin and their co-expression may predict FGFR-targeted therapy efficacy.

Álvaro Quintanal-Villalonga, Irene Ferrer, Elizabeth Guruceaga, Cristina Cirauqui, Ángela Marrugal, Laura Ojeda, Santiago García, Jon Zugazagoitia, Sandra Muñoz-Galván, Fernando Lopez-Rios, Luis Montuenga, Silvestre Vicent, Sonia Molina-Pinelo, Amancio Carnero, Luis Paz-Ares,

BACKGROUND:Fibroblast growth factor receptor (FGFR)1 and FGFR4 have been associated with tumorigenesis in a variety of tumour types. As a therapeutic approach, their inhibition has been attempted in different types of malignancies, including lung cancer, and was initially focused on FGFR1-amplified tumours, though with limited success. METHODS:In vitro and in ... Read more >>

EBioMedicine (EBioMedicine)
[2020, 53:102683]

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Genetic Mouse Models as In Vivo Tools for Cholangiocarcinoma Research.

Oihane Erice, Adrian Vallejo, Mariano Ponz-Sarvise, Michael Saborowski, Arndt Vogel, Diego F Calvisi, Anna Saborowski, Silvestre Vicent,

Cholangiocarcinoma (CCA) is a genetically and histologically complex disease with a highly dismal prognosis. A deeper understanding of the underlying cellular and molecular mechanisms of human CCA will increase our current knowledge of the disease and expedite the eventual development of novel therapeutic strategies for this fatal cancer. This endeavor ... Read more >>

Cancers (Basel) (Cancers)
[2019, 11(12):]

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Antitumor activity of an engineered decoy receptor targeting CLCF1-CNTFR signaling in lung adenocarcinoma.

Jun W Kim, Cesar P Marquez, Kaja Kostyrko, Amanda L Koehne, Kieren Marini, David R Simpson, Alex G Lee, Stanley G Leung, Leanne C Sayles, Joseph Shrager, Irene Ferrer, Luis Paz-Ares, Melanie Hayden Gephart, Silvestre Vicent, Jennifer R Cochran, E Alejandro Sweet-Cordero,

Proinflammatory cytokines in the tumor microenvironment can promote tumor growth, yet their value as therapeutic targets remains underexploited. We validated the functional significance of the cardiotrophin-like cytokine factor 1 (CLCF1)-ciliary neurotrophic factor receptor (CNTFR) signaling axis in lung adenocarcinoma (LUAD) and generated a high-affinity soluble receptor (eCNTFR-Fc) that sequesters CLCF1, ... Read more >>

Nat. Med. (Nature medicine)
[2019, 25(11):1783-1795]

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Experimental models to unravel the molecular pathogenesis, cell of origin and stem cell properties of cholangiocarcinoma.

Silvestre Vicent, Ruby Lieshout, Anna Saborowski, Monique M A Verstegen, Chiara Raggi, Stefania Recalcati, Pietro Invernizzi, Luc J W van der Laan, Domenico Alvaro, Diego F Calvisi, Vincenzo Cardinale,

Human cholangiocarcinoma (CCA) is an aggressive tumour entity arising from the biliary tree, whose molecular pathogenesis remains largely undeciphered. Over the last decade, the advent of high-throughput and cell-based techniques has significantly increased our knowledge on the molecular mechanisms underlying this disease while, at the same time, unravelling CCA complexity. ... Read more >>

Liver Int. (Liver international : official journal of the International Association for the Study of the Liver)
[2019, 39 Suppl 1:79-97]

Cited: 2 times

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Targeting of TMPRSS4 sensitizes lung cancer cells to chemotherapy by impairing the proliferation machinery.

Francisco Exposito, Maria Villalba, Miriam Redrado, Arrate L de Aberasturi, Cristina Cirauqui, Esther Redin, Elizabeth Guruceaga, Carlos de Andrea, Silvestre Vicent, Daniel Ajona, Luis M Montuenga, Ruben Pio, Alfonso Calvo,

High mortality rates caused by NSCLC show the need for the identification of novel therapeutic targets. In this study we have investigated the biological effects and molecular mechanisms elicited by TMPRSS4 in NSCLC. Overexpression of TMPRSS4 in LKR13 cells increased malignancy, subcutaneous tumor growth and multiorganic metastasis. In conditional knock-down (KD) ... Read more >>

Cancer Lett. (Cancer letters)
[2019, 453:21-33]

Cited: 2 times

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Inhibitor of Differentiation-1 Sustains Mutant KRAS-Driven Progression, Maintenance, and Metastasis of Lung Adenocarcinoma via Regulation of a FOSL1 Network.

Marta Román, Inés López, Elisabeth Guruceaga, Iosune Baraibar, Margarita Ecay, María Collantes, Ernest Nadal, Adrián Vallejo, Silvia Cadenas, Marta Echavarri-de Miguel, Jae Hwi Jang, Patxi San Martin-Uriz, Laura Castro-Labrador, Amaia Vilas-Zornoza, David Lara-Astiaso, Mariano Ponz-Sarvise, Christian Rolfo, Edgardo S Santos, Luis E Raez, Simona Taverna, Carmen Behrens, Walter Weder, Ignacio I Wistuba, Silvestre Vicent, Ignacio Gil-Bazo,

Because of the refractory nature of mutant KRAS lung adenocarcinoma (LUAD) to current therapies, identification of new molecular targets is essential. Genes with a prognostic role in mutant KRAS LUAD have proven to be potential molecular targets for therapeutic development. Here we determine the clinical, functional, and mechanistic role of ... Read more >>

Cancer Res. (Cancer research)
[2019, 79(3):625-638]

Cited: 2 times

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Blockade of the Complement C5a/C5aR1 Axis Impairs Lung Cancer Bone Metastasis by CXCL16-mediated Effects.

Daniel Ajona, Carolina Zandueta, Leticia Corrales, Haritz Moreno, María J Pajares, Sergio Ortiz-Espinosa, Elena Martínez-Terroba, Naiara Perurena, Fernando J de Miguel, Eloisa Jantus-Lewintre, Carlos Camps, Silvestre Vicent, Jackeline Agorreta, Luis M Montuenga, Ruben Pio, Fernando Lecanda,

RATIONALE:C5aR1 (CD88), a receptor for complement anaphylatoxin C5a, is a potent immune mediator. Its impact on malignant growth and dissemination of non-small cell lung cancer cells is poorly understood. OBJECTIVES:To investigate the contribution of the C5a/C5aR1 axis to the malignant phenotype of non-small cell lung cancer cells, particularly in skeletal ... Read more >>

Am. J. Respir. Crit. Care Med. (American journal of respiratory and critical care medicine)
[2018, 197(9):1164-1176]

Cited: 6 times

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Adjuvant Therapy for Colon Cancer: Genes, Genes… and the Patient in the Center.

Javier Rodriguez, Silvestre Vicent, Ana Chopitea, Mariano Ponz-Sarvisé,

Although molecular subtype-based stratification and genomic signatures of increasing complexity are becoming a new strategy to guide therapeutic decisions in stage II/III colon cancer, several prognostic factors that can be easily obtained from formalin-fixed paraffin-embedded (FFPE) specimens should be considered to create combined models that better define individual patients' needs. ... Read more >>

Clin. Cancer Res. (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2018, 24(16):3787-3789]

Cited: 0 times

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KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target.

Marta Román, Iosune Baraibar, Inés López, Ernest Nadal, Christian Rolfo, Silvestre Vicent, Ignacio Gil-Bazo,

Lung neoplasms are the leading cause of death by cancer worldwide. Non-small cell lung cancer (NSCLC) constitutes more than 80% of all lung malignancies and the majority of patients present advanced disease at onset. However, in the last decade, multiple oncogenic driver alterations have been discovered and each of them ... Read more >>

Mol. Cancer (Molecular cancer)
[2018, 17(1):33]

Cited: 20 times

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All for one and FOSL1 for all: FOSL1 at the crossroads of lung and pancreatic cancer driven by mutant KRAS.

Adrian Vallejo, Karmele Valencia, Silvestre Vicent,

KRAS proto-oncogene, GTPase (KRAS) remains refractory to current therapies. We devised an integrative cross-tumor approach to expose common core elements up-regulated in mutant KRAS cancers that could provide new treatment opportunities. This approach identified FOSL1 (Fos-like antigen 1) as a clinically and functionally relevant gene in mutant KRAS-driven lung and ... Read more >>

Mol Cell Oncol (Molecular & cellular oncology)
[2017, 4(3):e1314239]

Cited: 1 time

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A Combined PD-1/C5a Blockade Synergistically Protects against Lung Cancer Growth and Metastasis.

Daniel Ajona, Sergio Ortiz-Espinosa, Haritz Moreno, Teresa Lozano, María J Pajares, Jackeline Agorreta, Cristina Bértolo, Juan J Lasarte, Silvestre Vicent, Kai Hoehlig, Axel Vater, Fernando Lecanda, Luis M Montuenga, Ruben Pio,

Disruption of the programmed cell death protein 1 (PD-1) pathway with immune checkpoint inhibitors represents a major breakthrough in the treatment of non-small cell lung cancer. We hypothesized that combined inhibition of C5a/C5aR1 and PD-1 signaling may have a synergistic antitumor effect. The RMP1-14 antibody was used to block PD-1, ... Read more >>

Cancer Discov (Cancer discovery)
[2017, 7(7):694-703]

Cited: 32 times

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EPCR promotes breast cancer progression by altering SPOCK1/testican 1-mediated 3D growth.

Naiara Perurena, Carolina Zandueta, Susana Martínez-Canarias, Haritz Moreno, Silvestre Vicent, Ana S Almeida, Elisabet Guruceaga, Roger R Gomis, Marta Santisteban, Mikala Egeblad, José Hermida, Fernando Lecanda,

BACKGROUND:Activated protein C/endothelial protein C receptor (APC/EPCR) axis is physiologically involved in anticoagulant and cytoprotective activities in endothelial cells. Emerging evidence indicates that EPCR also plays a role in breast stemness and human tumorigenesis. Yet, its contribution to breast cancer progression and metastasis has not been elucidated. METHODS:Transcriptomic status of ... Read more >>

J Hematol Oncol (Journal of hematology & oncology)
[2017, 10(1):23]

Cited: 7 times

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Matrix-Gla protein promotes osteosarcoma lung metastasis and associates with poor prognosis.

Carolina Zandueta, Cristina Ormazábal, Naiara Perurena, Susana Martínez-Canarias, Marta Zalacaín, Mikel San Julián, Agamemnon E Grigoriadis, Karmele Valencia, Francisco J Campos-Laborie, Javier De Las Rivas, Silvestre Vicent, Ana Patiño-García, Fernando Lecanda,

Osteosarcoma (OS) is the most prevalent osseous tumour in children and adolescents and, within this, lung metastases remain one of the factors associated with a dismal prognosis. At present, the genetic determinants driving pulmonary metastasis are poorly understood. We adopted a novel strategy using robust filtering analysis of transcriptomic profiling ... Read more >>

J. Pathol. (The Journal of pathology)
[2016, 239(4):438-449]

Cited: 13 times

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The present and the future of the RAS pathway: From function and genomics to inhibition.

Ignacio Gil-Bazo, Alejandro Sweet-Cordero, Silvestre Vicent,

This meeting report summarizes the highlights of the II International Frontiers in Oncology meeting "The present and future of the RAS pathway: from function and genomics to inhibition" (RAS Frontiers) organized by the Center for Applied Medical Research (CIMA; Pamplona, SPAIN), the Clinic of the University of Navarra (CUN; Pamplona, ... Read more >>

Cancer Biol. Ther. (Cancer biology & therapy)
[2016, 17(7):719-722]

Cited: 2 times

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Bone metastases in lung cancer. Potential novel approaches to therapy.

Silvestre Vicent, Naiara Perurena, Ramaswamy Govindan, Fernando Lecanda,

The skeleton is a common site of metastases in lung cancer, an event associated with significant morbidities and poor outcomes. Current antiresorptive therapies provide limited benefit, and novel strategies of prevention and treatment are urgently needed. This review summarizes the latest advances and new perspectives on emerging experimental and clinical ... Read more >>

Am. J. Respir. Crit. Care Med. (American journal of respiratory and critical care medicine)
[2015, 192(7):799-809]

Cited: 6 times

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A meta-analysis of lung cancer gene expression identifies PTK7 as a survival gene in lung adenocarcinoma.

Ron Chen, Purvesh Khatri, Pawel K Mazur, Melanie Polin, Yanyan Zheng, Dedeepya Vaka, Chuong D Hoang, Joseph Shrager, Yue Xu, Silvestre Vicent, Atul J Butte, E Alejandro Sweet-Cordero,

Lung cancer remains the most common cause of cancer-related death worldwide and it continues to lack effective treatment. The increasingly large and diverse public databases of lung cancer gene expression constitute a rich source of candidate oncogenic drivers and therapeutic targets. To define novel targets for lung adenocarcinoma, we conducted ... Read more >>

Cancer Res. (Cancer research)
[2014, 74(10):2892-2902]

Cited: 53 times

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RHOB influences lung adenocarcinoma metastasis and resistance in a host-sensitive manner.

Diego Luis-Ravelo, Iker Antón, Carolina Zandueta, Karmele Valencia, María-José Pajares, Jackeline Agorreta, Luis Montuenga, Silvestre Vicent, Ignacio I Wistuba, Javier De Las Rivas, Fernando Lecanda,

Lung adenocarcinoma (ADC) is the most common lung cancer subtype and presents a high mortality rate. Clinical recurrence is often associated with the emergence of metastasis and treatment resistance. The purpose of this study was to identify genes with high prometastatic activity which could potentially account for treatment resistance. Global ... Read more >>

Mol Oncol (Molecular oncology)
[2014, 8(2):196-206]

Cited: 13 times

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Cross-species functional analysis of cancer-associated fibroblasts identifies a critical role for CLCF1 and IL-6 in non-small cell lung cancer in vivo.

Silvestre Vicent, Leanne C Sayles, Dedeepya Vaka, Purvesh Khatri, Olivier Gevaert, Ron Chen, Yanyan Zheng, Anna K Gillespie, Nicole Clarke, Yue Xu, Joseph Shrager, Chuong D Hoang, Sylvia Plevritis, Atul J Butte, E Alejandro Sweet-Cordero,

Cancer-associated fibroblasts (CAF) have been reported to support tumor progression by a variety of mechanisms. However, their role in the progression of non-small cell lung cancer (NSCLC) remains poorly defined. In addition, the extent to which specific proteins secreted by CAFs contribute directly to tumor growth is unclear. To study ... Read more >>

Cancer Res. (Cancer research)
[2012, 72(22):5744-5756]

Cited: 33 times

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Twist1 suppresses senescence programs and thereby accelerates and maintains mutant Kras-induced lung tumorigenesis.

Phuoc T Tran, Emelyn H Shroff, Timothy F Burns, Saravanan Thiyagarajan, Sandhya T Das, Tahera Zabuawala, Joy Chen, Yoon-Jae Cho, Richard Luong, Pablo Tamayo, Tarek Salih, Khaled Aziz, Stacey J Adam, Silvestre Vicent, Carsten H Nielsen, Nadia Withofs, Alejandro Sweet-Cordero, Sanjiv S Gambhir, Charles M Rudin, Dean W Felsher,

KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors ... Read more >>

PLoS Genet. (PLoS genetics)
[2012, 8(5):e1002650]

Cited: 54 times

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MEK1/2 inhibition elicits regression of autochthonous lung tumors induced by KRASG12D or BRAFV600E.

Christy L Trejo, Joseph Juan, Silvestre Vicent, Alejandro Sweet-Cordero, Martin McMahon,

Genetically engineered mouse (GEM) models of lung tumorigenesis allow careful evaluation of lung tumor initiation, progression, and response to therapy. Using GEM models of oncogene-induced lung cancer, we show the striking similarity of the earliest stages of tumorigenesis induced by KRAS(G12D) or BRAF(V600E). Cre-mediated expression of KRAS(G12D) or BRAF(V600E) in ... Read more >>

Cancer Res. (Cancer research)
[2012, 72(12):3048-3059]

Cited: 33 times

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Tumor-stromal interactions of the bone microenvironment: in vitro findings and potential in vivo relevance in metastatic lung cancer models.

Diego Luis-Ravelo, Iker Antón, Silvestre Vicent, Igor Hernández, Karmele Valencia, Carolina Zandueta, Susana Martínez-Canarias, Alfonso Gúrpide, Fernando Lecanda,

Lung cancer comprises a large variety of histological subtypes with a frequent proclivity to form bone metastasis; a condition associated with dismal prognosis. To identify common mechanisms in the development of osteolytic metastasis, we systematically screened a battery of lung cancer cell lines and developed three models of non-small cell ... Read more >>

Clin. Exp. Metastasis (Clinical & experimental metastasis)
[2011, 28(8):779-791]

Cited: 10 times

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Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models.

Silvestre Vicent, Ron Chen, Leanne C Sayles, Chenwei Lin, Randal G Walker, Anna K Gillespie, Aravind Subramanian, Gregory Hinkle, Xiaoping Yang, Sakina Saif, David E Root, Vicki Huff, William C Hahn, E Alejandro Sweet-Cordero,

KRAS is one of the most frequently mutated human oncogenes. In some settings, oncogenic KRAS can trigger cellular senescence, whereas in others it produces hyperproliferation. Elucidating the mechanisms regulating these 2 drastically distinct outcomes would help identify novel therapeutic approaches in RAS-driven cancers. Using a combination of functional genomics and ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2010, 120(11):3940-3952]

Cited: 74 times

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A novel lung cancer signature mediates metastatic bone colonization by a dual mechanism.

Silvestre Vicent, Diego Luis-Ravelo, Iker Antón, Ignacio García-Tuñón, Francisco Borrás-Cuesta, Javier Dotor, Javier De Las Rivas, Fernando Lecanda,

Bone is a frequent target of lung cancer metastasis, which is associated with significant morbidity and a dismal prognosis. To identify and functionally characterize genes involved in the mechanisms of osseous metastasis, we developed a murine lung cancer model. Comparative transcriptomic analysis identified genes encoding signaling molecules (such as TCF4 ... Read more >>

Cancer Res. (Cancer research)
[2008, 68(7):2275-2285]

Cited: 42 times

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