Oncology

Molecular Pathology of Cancer

Molecular Pathology of Cancer

The Cancer Molecular Pathology Research Unit is composed of researchers from Navarrabiomed and clinical researchers from the Pathology Department, Surgery and other services at the University Hospital of Navarra. Its fundamental objective is the detection of new genetic and epigenetic biomarkers related to prognosis and response to oncological treatment in patients with different types of cancer, mainly breast cancer, colorectal cancer, gynecological cancers, and brain tumors among others. For this, we use massively parallel sequencing (NGS) on tissue and liquid biopsy, as well as single-gene molecular techniques such as pyrosequencing, real-time PCR, etc.

The unit collaborates with other research groups at Navarrabiomed and at other institutions (IUOPA, Oviedo; PEBC-IDIBELL, Barcelona).


Research lines:

  1. Analysis of aberrant methylation (hypo- and hypermethylation) and presence of alterations (mutations, indels, copy number variations, fusions) in genes involved in the progression of solid tumors.
  2. Analysis of the prognostic and predictive value of these biomarkers for response to oncological treatment.
  3. Analysis of protein expression profiles in relation to tumor characteristics.
  4. In vitro functional assays.
     

 

Investigador principal
Equipo de investigadores
Área de investigación
Oncology
Molecular Pathology of Cancer
Actualidad

Saioa Mendaza Lainez defenderá su tesis doctoral el martes, 30 de junio

Author
Navarrabiomed

Saioa Mendaza Lainez, investigadora predoctoral en la Unidad de Patología Molecular del Cáncer de Navarrabiomed, realizará la lectura de su tesis doctoral por la Universidad Pública de Navarra el martes 30 de junio, a las 11:30, a través de videoconferencia en Navarrabiomed (solamente podrán acudir aquellas personas autorizadas previamente). 

La tesis, titulada Approaching the epigenome of triple-negative breast cancer to identify new biomarkers, ha sido desarrollada en Navarrabiomed bajo la dirección del Dr. David Guerrero Setas y la Dra. Esperanza Martín Sánchez.


El cáncer de mama es la neoplasia más frecuente en mujeres a nivel mundial y la primera causa de muerte por cáncer en este mismo sexo. La investigación aborda el cáncer de mama triple negativo (CMTN), un subtipo que a diferencia del resto carece de tratamiento dirigido, lo que conlleva consecuencias más agresivas en las personas que lo padecen. Esto hace que a día de hoy, la búsqueda de nuevos biomarcadores y dianas terapéuticas para esta enfermedad sea imprescindible.

Dado que las alteraciones epigenéticas están involucradas en la tumorigénesis, el objetivo de esta tesis ha sido caracterizar la metilación del DNA y la acetilación de histonas de este tipo de cáncer. Con ello se ha buscado identificar nuevas firmas potencialmente diagnósticas y pronósticas, así como alteraciones destinatarias de fármacos dirigidos.

Los resultados de esta caracterización han permitido concluir que el patrón epigenético está alterado en CMTN respecto a tejido mamario no neoplásico. Más importante aún, la investigación ha desvelado dos alteraciones epigenéticas específicas como potenciales biomarcadores de peor pronóstico: la acetilación de la histona H4K5 y la hipometilación del gen ADAM12, el cual se presenta también como posible diana terapéutica frente a este cáncer.

Asimismo, se ha identificado una nueva firma basada en metilación de DNA con utilidad diagnóstica. Por último, se han descrito los procesos biológicos de los distintos genes regulados por la acetilación de H4K6 en líneas celulares no neoplásicas y CMTN.

El trabajo realizado ha dado lugar a tres publicaciones científicas y ha sido difundido en dos congresos consecutivos de European Association for Cancer Research; uno celebrado en Manchester en el año 2017 y en Amsterdam en el 2018.

Para el desarrollo de la tesis Saioa Mendaza ha sido beneficiaria de dos becas: Ayudas para la formación de Personal Investigador de la Univesidad Pública de Navarra  para la realización de tesis doctorales y Beca a la excelencia de la Funcación Caja Navarra para la realización de una estancia en University of Massachussets Medical School (EEUU).

Categoría
Vídeo
Colaboradores/as
Amat Villegas, Irene
Hospital Universitario de Navarra
Armendáriz Rubio, Pedro
Hospital Universitario de Navarra
Arriola Osés, Marta
Hospital Universitario de Navarra
Córdoba Iturriagagoitia, Alicia
Hospital Universitario de Navarra
Guarch Troyas, Rosa
Hospital Universitario de Navarra
Ruiz de Azua Ciria, Ana Yerani
Hospital Universitario de Navarra
Zazpe Cenoz, Idoya
Hospital Universitario de Navarra
Unidad de investigación / Grupo Vinculado
Contacto
Molecular Pathology of Cancer

Navarrabiomed - Centro de investigación biomédica
Complejo Hospitalario de Navarra, edificio de investigación.
Calle Irunlarrea, 3. 31008 Pamplona, Navarra, España. 

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Cancer Signalling

Cancer Signalling

The Cancer Signaling Unit is interested in understanding the molecular mechanisms by which cancer cells develop resistance to targeted therapies currently used to treat oncology patients. To that end we have developed three research lines focused on melanoma, glioblastoma, and triple-negative breast cancer. By blocking these adaptive resistance mechanisms, we aim to improve the therapeutic efficacy of treatments such as radiotherapy, targeted therapies, and immunotherapies. The unit's ultimate goal is to translate its results into clinical practice.

Investigador principal
Área de investigación
Oncology
Drug resistance and metastasis
Actualidad

Metabolic rewiring induced by ranolazine improves melanoma responses to targeted therapy and immunotherapy

En verde la tinción de los linfocitos antitumorales tipo NK y en azul, las células tumorales.  ➡️ El tratamiento con #ranolazina aumenta la cantidad de linfocitos antitumorales que infiltran el tumor y favorecen la acción de la inmunoterapia.
Author
Navarrabiomed

A study led by Navarrabiomed proposes a therapeutic alternative to treat melanoma.

  • The drug ranolazine, used to treat chronic angina pectoris, could improve response to anti-melanoma therapies.
  • This is a multicenter investigation carried out by Navarrabiomed biomedical research center, the Institute for Neurosciences CSIC-UMH, and IRB Barcelona.

The prestigious journal Nature Metabolism has published the results of a study in mice that determined that ranolazine, a drug that is currently administered to patients to treat heart conditions, delays the appearance of resistance to melanoma treatments, by blocking fatty acids metabolism. This research has been led by Navarrabiomed, together with the Institute for Neurosciences (CSIC-UMH) and IRB Barcelona. Melanoma is the most aggressive type of skin cancer and, although it only accounts for 10% of skin cancer cases, it is responsible for 90% of deaths associated with skin tumours. Thanks to the development of targeted therapies and immunotherapies, the clinical management of patients affected with this type of cancer has improved, however, these therapies still have limitations because 50% of patients do not respond adequately and even develop resistance.

The evidence suggests that this resistance could be linked to metabolic reprogramming in cancer cells that is associated to changes in the way in which cells process and use nutrients. This research demonstrates that fatty acid metabolism plays an important role in the development of resistance to melanoma treatments.

Researchers have confirmed that increased fatty acid oxidation occurs during long-term treatment with BRAF inhibitors, one of the key genes in tumour progression, contributing to therapy resistance.

Ranolazine increases the efficacy of targeted therapy against melanoma because it can target fatty acid oxidation. In addition, the application of this drug promotes that melanoma cells become more visible to the immune system,improving the response to immunotherapies and increasing the ability of lymphocytes to control tumour growth.

A multicenter investigation

The Navarrabiomed Cancer Signaling Unit, directed by Imanol Arozarena Martinicorena, has coordinated the course of the research and has been in charge of carrying out the experiments related to resistance to targeted therapies and the study of how ranolazine affects the immunogenicity of melanoma cells.

Researchers at the laboratory led by Berta Sánchez-Laorden, belonging to the Cell Plasticity in Development and Disease group at the Institute for Neurosciences, have developed immunotherapy experiments in mice and have carried out the study of immune cells in the tumour microenvironment.

In addition, the IRB Barcelona Stem Cells and Cancer research group, led by Salvador Aznar-Benitah, has carried out individual cell RNA sequencing analyses, which have made it possible to find out in detail the effect of the drug on the state metabolism of tumour cells.

Funding

This study, which has been made possible thanks to funding granted by the Ministry of Science and Innovation, the Carlos III Health Institute, the Government of Navarra, the Spanish Multidisciplinary Melanoma Group (GEM), and the Melanoma Research Alliance, is a clear example of how basic research can contribute a lot to the repositioning of drugs, which makes it possible to significantly shorten the deadlines for providing answers to patients suffering from diseases as prevalent as cancer.

Categoría
Galería de imágenes
Marta Redondo and Imanol Arozarena, responsible for this research in Navarrabiomed
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Single cell sequencing analysis of different immune populations infiltrating untreated melanoma tumors or treated with ranolazine (Rano), immunotherapy (PDL1) or the combination of both (PDL1+Rano).
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Treatment with ranolazine increases the number of antitumour lymphocytes (green) that infiltrate the tumour(b lue) and favour the action of immunotherapy
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Documentación
Vídeo

SARAY funds Navarrabiomed with 46,970 euros for two projects on metastatic breast cancer

Author
Navarrabiomed
  • Since 2015 the associations annual investment in research has been increased by 65%


On October 27th, 2019 Breast Cancer Association of Navarre SARAY collected 75,000 euros in the solidarity race celebrated in Pamplona. 49,970 euros will fund two studies developed by Navarrabiomed on metastatic breast cancer.

One of the projects is focused on liquid biopsy in this type of cancer, and it is led by Natalia Ramírez Huerto, the head of the Hematological Oncology Unit of Navarrabiomed. SARAY´s contribution for the second year of the project development raises to 24,970 euros. Other study lead by Cancer Signaling Unit head Imanol Arozarena Martinicorena will receive 22,000 euros. His project aims to develop new adjuvant therapies to treat brain and bone metastases from these tumors. The additional funds will be donated to the Chronos Hope Project from Solti Foundation.

On the 25th of June SARAY decided to allocate the incomes in a face-to-face and online assembly among 725 associates (event delayed three months later due to the COVID-19 crisis). During the last years, the organization shows a strong commitment with biomedical research performed in Navarre. Therefore, it is relevant to highlight that since 2015 SARAY has increased by 65% its annual investment in oncology research.

 

Categoría
Galería de imágenes
Natalia Ramírez Huerto, investigadora principal de la Unidad de Oncohematología
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Imanol Arozarena Martinicorena, investigador principal de la Unidad de Señalización en Cáncer
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Documentación
Vídeo

Navarrabiomed and University of Manchester researchers publish melanoma review in Nature

Author
Navarrabiomed

Imanol Arozarena, senior researcher from the Cancer Signalling Unit at the Navarrabiomed biomedical research centre and a member of Instituto de Investigación Sanitaria de Navarra (IdiSNA), has recently published a melanoma review with University of Manchester Professor Claudia Wellbrock.

The two scientists were asked by the renowned scientific journal Nature Reviews: Cancer to write an article on the latest findings in melanoma cell distinct phenotypes and their relevance for melanoma development and response to therapy.

As many as 4000 new melanoma cases are diagnosed in Spain every year. Malignant melanoma is a serious type of skin cancer that is usually metastatic. It is notorious for its intra- and inter-tumour heterogeneity.

Such variability results from the ability of melanoma cells (melanocytes) to adjust to changing environmental conditions by reprogramming their genetic expression. Thus, melanocytes develop resistance to both targeted therapy and immunotherapy, and their plasticity plays a role in metastasis development.

In their article, the authors reveal the importance of combining recent developments in genomic technologies and the availability of large gene expression datasets for a precise definition of the gene signatures that characterise changes in each patient’s tumours and the prognostic relevance for tumour development and response to therapy.

According to Arozarena, ‘By understanding the molecular mechanisms that adapt melanoma cells to anti-tumour drugs, we will be able to prevent both therapy resistance and the progression of metastatic melanoma.

Categoría
Galería de imágenes
Los autores, Arozarena y Wellbrock
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Colaboraciones Logotipos
Vídeo
I-Gliome
I-Gliome
Imanol
Arozarena Martinicorena
Head of the Unit
Visor 360º
360º Virtual Tour
Cancer Signalling
Lab
Colaboradores/as
Wellbrock, Claudia
Universidad Pública de Navarra
Rico Oses, Mikel
Hospital Universitario de Navarra
Zazpe Cenoz, Idoya
Hospital Universitario de Navarra
Larrayoz, Iñaki
Universidad de la Rioja
Labiano, Sara
CIMA
Lecanda, Fernando
CIMA
Aznar Benitah, Salvador
IRB-Barcelona
Unidad de investigación / Grupo Vinculado
Contacto
Cancer Signalling

Navarrabiomed - Centro de investigación biomédica
Complejo Hospitalario de Navarra, edificio de investigación.
Calle Irunlarrea, 3. 31008 Pamplona, Navarra, España. 

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