Vés al contingut

Aroa Soriano Fernández

Institucions de les que formen part

Investigador/a principal
Càncer i malalties hematològiques infantils
Vall Hebron Institut de Recerca

Aroa Soriano Fernández

Institucions de les que formen part

Investigador/a principal
Càncer i malalties hematològiques infantils
Vall Hebron Institut de Recerca

Línies de recerca

Program of Personalized Medicine


Principal Investigator:

Aroa Soriano, PhD & Lucas Moreno, MD, PhD


Research Team:

- Raquel Hladun, MD: PhD researcher and Pediatric Oncologist

- Gabriela Guillén, MD: PhD researcher and Pediatric Surgeon

- Ainara Magdaleno: Laboratory Technician

- Lorena Valero, MD: Pediatric Oncologist

- Andrea Vilaplana: Biologist

- Alba Fernández, MD: Pediatric Oncologist


Collaborators or Associated Researchers or Clinical Associated Researchers:

- Luís Gros, MD: Pediatric Oncologist

- Anna Llort, MD, PhD: Pediatric Oncologist

- Constantino Sábado, MD, PhD: Pediatric Oncologist

- Maria Paula Pérez, MD: Pediatric Oncologist

- Marta Sesé, PhD: Biologist

- Javier Hernández, PhD: Biologist

- Elena Martínez, MD, PhD: Pathologist

- Marta Garrido, MD: Pathologist

- Alexandra Navarro, MD: Pathologist

- Jessica Camacho, MD, PhD: Pathologist

- Josep Roma, PhD: Sarcoma Lab PI

- Miguel Segura, PhD: Neural Tumors PI

- José Andrés Molino, MD: Pediatric Surgeon

- Sergio López, MD: Pediatric Surgeon

- Mª Antonia Poca: Pediatric Neurosurgeon

- Katiuska Rosas: Pediatric Neurosurgeon

- Diego Fernando Lopez: Pediatric Neurosurgeon

- Josefa Elida Vázquez: Radiologists

- Luis Riera: Radiologists

- Ana Coma: Radiologists

- Joan Albert Prat: Radiologists

- Angel Sánchez-Montañez: Radiologists

- José Miguel Escudero: Radiologists

- Lucia Riaza: Radiologists

- Ignacio Delgado: Radiologists


BACKGROUND


Revolution of Personalized Medicine in cancer care: The recent advances of anticancer precision medicine drugs have changed the paradigm of cancer treatment, particularly in tumors with single driving genetic alteration or oncogene addiction. Some of the most prominent examples of targeted drugs in pediatric cancers include NTRK, BRAF or ALK inhibitors. These novel drugs have completely changed frontline treatment practice for small subgroups of patients across tumor types, which need to be identified upfront.

Deep molecular profiling helps to improve diagnosis, and molecular diagnostics is already included in many childhood cancer entities in the WHO classification. Moreover, it refines prognostic stratification by identifying poor/good prognosis subgroups which need different treatments. In addition, it allows the identification of cancer predisposition syndromes which have major implications in management and surveillance, not only for the patients but also for their families.

The main goal of our Personalized Medicine Program is to build, implement and consolidate a strong personalized medicine program based on molecular profiling approaches to improve diagnosis accuracy, prognosis, treatment and identification of cancer predisposition syndromes for all children and adolescents with cancer in Spain. Our final aim is to offer every child with cancer the best possible chance of survival.

The personalised medicine program consists of a true multidisciplinary team formed by pediatric oncologists, surgeons, pathologists, radiologists, geneticists, molecular translational researchers and bioinformaticians who are committed to their work.

Our group also works in several Data Science projects, particularly focused in neuroblastoma. The genomic data generated in sequencing programs (COMIK, MAPPYACTS among others) together with clinical data generated within clinical trials (such as BEACON) and through the INRG collaboration (www.inrgdb.org) is further analysed and combined to identify novel biomarkers and targets that can be implemented in the clinic; also in collaboration with international data sharing initiatives.


RESEARCH STRATEGY AND SCOPE


The Pediatric Oncology Personalized Medicine Program is composed of:

COMIK (Cancer OMIcs for Kids) Program

• COMIK is the personalised medicine program of Vall d’Hebron Hospital for children, adolescents and young adults with relapsed/refractory solid tumours. COMIK includes patients from all the autonomous communities. Within COMIK programme we perform whole exome sequencing (WES) and RNA sequencing to obtain the complete profile of molecular alterations of the patients’ tumors to improve the access of children and adolescents with cancer to innovative therapies and targeted therapies within basket clinical trials. Our pre-screening platform is the only one in Spain based on WES and RNAseq molecular profiling.

• Functional Screening: Clinical pediatric precision oncology platforms have already identified actionable molecular targets in approximately 60% of pediatric cancers by applying next generation sequencing technologies. Despite the immense knowledge generated through sequencing efforts the remaining 40% of the children and adolescents lack actionable alterations indicating significant currently unmet needs in precision medicine programs. New targets and combinations must be identified combining profiling with functional data. We want to integrate the results of deep molecular profiling with novel functional screening tools, to increase and improve the therapeutic options available for pediatric patients.

• PDOX (Patient-derived orthotopic xenografts): COMIK program includes the generation of PDOX. Currently, we have established 50 orthotopic PDX models of pediatric solid tumors in collaboration with Dr. Alberto Villanueva from ICO/IDIBELL. Primary tumors and metastases from different locations were surgically grafted in their original locations in immunocompromised mice, maintaining their three-dimensional tissue structure. PDOX are unique valuable tools for

pediatric drug development, the discovery of molecular mechanisms for drug efficacies and combinations and in personalized medicine programs.

SEHOP-PENCIL (Personalised Medicine for Cancer in Children in Spain) Program

While France, the UK or Germany have now implemented routine next generation sequencing (NGS) panels and WES and RNAseq for all childhood cancer patients at diagnosis and relapse, sequencing has not yet been widely incorporated by the Spanish health care system for pediatric cancer patients. SEHOP-PENCIL is the Precision Medicine Strategy of our national scientific society (SEHOP-Sociedad Española de Hematología y Oncología Pediátrica) to create a network of eight hubs, all of which will be accessible to all hospitals treating pediatric cancer patients across our territory.

We want to implement molecular profiling approaches to improve diagnosis accuracy, treatment and identification of cancer predisposition syndromes for all children and adolescents with cancer in Spain. Moreover, we want to evaluate the efficacy and cost-effectiveness of these personalized medicine approaches and facilitate the regulatory and administrative pathway for their introduction in clinical care in the Spanish national healthcare system, ensuring equity and excellence in care for Spanish children and adolescents with cancer.

MAPPYACTS (MoleculAr Profiling for Pediatric and Young Adult Cancer Treatment Stratification)

We have also collaborated in a European study of personalised medicine in paediatric cancer called MAPPYACTS. MAPPYACTS is a world-leading personalised medicine program that has changed the model of care for children with cancer in France. Vall d’Hebron was the only hub outside France accredited for genomic analyses of Spanish patients within this trial. Our participation in MAPPYACTS2 will start during 2022.


ONGOING COMPETITIVE PROJECTS:


• PI21/01661 (AES-ISCIII)- PI: Lucas Moreno & Aroa Soriano. COMIK 2.0: Integration of a genomic and functional screening platform for pediatric precision oncology. From 2022 to 2024. Amount granted: 214.170 €.

Our group started the personalized medicine program COMIK in 2016-2017, which has conducted WES in more than 100 pediatric patients to date. The program included patients with high-risk, refractory and relapsed solid tumours in the Paediatric Haematology & Oncology Unit of the Vall d'Hebron Hospital. COMIK2.0 is to enlarge the COMIK project including functional testing in addition to WES & RNASeq and facilitating referrals from all centres in Spain.

Nowadays, molecular screening is mandatory for 14 early phase trials in Spain and 4 of them require deep genomic screening with WES/WGS/RNAseq (i.e AcSe-ESMART [EudraCT 2016-000133-40]) Our main goal in this project is the development of a pre-screening platform for pediatric basket trials for relapsed & refractory childhood and adolescent cancers to maximize chances of antitumor efficacy and increase access of the pediatric patients to innovative therapies.

We also propose to integrate molecular analyses with a functional screening assay to improve the ability to predict clinical benefit of therapeutic options for pediatric patients. Functional screening assays perfectly complement molecular analysis in personalized medicine platforms when actionable alterations are not found or when we identify multiple genetic alterations. Our goal is to develop more accurate predictive pre-screening methods to offer the best therapeutic option for pediatric patients with relapsed and refractory tumors.

• PMP21/00073 (AES-ISCIII)-PI: Lucas Moreno. SEHOP-PENCIL Study: Personalised Medicine for Cancer in Children in Spain. From 2022 to 2025. Total amount: 1.890.703 €. VHIR coordinating group: 1.025.179,10

Incorporating high level personalized medicine programs in standard treatment of childhood cancer offers a unique opportunity to improve survival and reduce morbidities for all children.

The PENCIL project by the Spanish Society of Paediatric Haematology and Oncology has four major objectives: 1) To implement a nation-wide sequencing program offering access to next generation sequencing (NGS) panels at the time of diagnosis for high-risk cancers, whole exome/whole-genome sequencing (WES/WGS) and RNASeq at relapse, germline NGS panel or WGS to identify cancer predisposition syndromes and DNA methylation profiling for CNS tumours and sarcomas. 2) To develop tools to facilitate access to PerMed to all patients across Spain, by creating a network of clinicians and genomic hubs and molecular tumour boards. 3) To evaluate the implementation of PerMed into routine care for childhood cancer including cost-effectiveness and clinical outcomes. 4) To develop novel technologies that will overcome current limitations of diagnostic and surveillance approaches, such as liquid biopsy. The incorporation of PerMed into routine care will lead to improved diagnostic and prognostic information at diagnosis, increased access to novel targeted therapies at relapse and early identification and intervention on cancer predisposition syndromes for patients in all autonomous regions of Spain, resulting in major benefits for our society.

BEACON-BIO (Fights Kids Cancer)-IP: Lucas Moreno. Total amount:104.500 € VHIR coordinating group: 499.776 €

The BEACON trial (EudraCT 2012-000072-42) is a collaborative trial between the European consortia for early clinical trials and neuroblastoma research (ITCC and SIOPEN respectively)

for RRNB that started in 2013 that is now completed (n=225). In the first 160 patients, it evaluated three regimens (temozolomide, irinotecan-temozolomide and topotecantemozolomide) and bevacizumab (an anti-VEGF monoclonal antibody) showing improvements in response rates and survival, meeting trial pre-defined success criteria for progression-free survival (PFS). The Bevacizumab-Irinotecan-Temozolomide (BIT) combination may be more effective than irinotecan or bevacizumab separately: 2-year PFS was 49% for this arm. The trial was then amended to evaluate the addition of dinutuximab beta to topotecan-temozolomide chemotherapy following results from US trials with chemo-immunotherapy. 65 patients have been recruited and results will be available during Q4 2021 (Gray, Moreno & Wheatley). Currently, relapsed and refractory patients show different clinical phenotype and outcomes, but they are commonly grouped together in clinical trials. A crucial objective of this project will be to fully characterise these two populations.


SELECTED PUBLICATIONS (Top 10):


1. Berlanga P, Pierron G, Lacroix L, Chicard M, Adam de Beaumais T, Marchais A, Harttrampf AC, Iddir Y, Larive A, Soriano A, Hezam I, Chevassus C, Bernard V, Cotteret S, Scoazec JY, Gauthier A, Abbou S, Corradini N, André N, Aerts I, Thebaud E, Casanova M, Owens C, Hladun R, Michiels S, Delattre O, Vassal G, Schleiermacher G, Geoerger B. The European MAPPYACTS trial: Precision Medicine Program in Pediatric and Adolescent Patients with Recurrent Malignancies. Cancer Discovery 2022.

2. Gargallo P, Bautista F, Juan-Ribelles A, Izquierdo E, Soriano A, de Rojas T, Escudero A, Lavarino C, Solano P, Hladun R, Rubio-San-Simón A, Martínez-Romera I, Calabria I, Olaciregui NG, Castañeda-Heredia A, de Álava E, Pérez-Martínez A, Astigarraga I, Patiño-García A, Alonso J, Fernández-Teijeiro A, Cañete A & Moreno L. Current status of precision medicine in pediatric oncology in Spain: a consensus report by the Spanish Society of Paediatric Haematology and Oncology (SEHOP). Clinical and Translational Oncology. 2022 Feb. PMID: 35152364. DOI: 10.1007/s12094-021-02759-7.

3. Segura MF, Soriano A, Roma J, Piskareva O, Jiménez C, Boloix A, Fletcher JI, Haber M, Gray JC, Cerdá-Alberich L, Martínez de Las Heras B, Cañete A, Gallego S, Moreno L. Methodological advances in the discovery of novel neuroblastoma therapeutics. Expert Opin Drug Discov. 2022 Feb;17(2):167-179. doi: 10.1080/17460441.2022.2002297. Epub 2021 Nov 22. PMID: 34807782.

4. Masanas M, Masiá N, Suárez-Cabrera L, Olivan M, Soriano A, Majem B, Devis-Jauregui L, Burgos-Panadero R, Jiménez C, Rodriguez-Sodupe P, Boloix A, Toledano I, Guillén G, Navarro A, Llobet-Navas D, Villanueva A, Sánchez de Toledo J, Roma J, Noguera R, Moreno L, Krauss R, Gallego S, Santamaria A*, Segura MF*. The oral KIF11 inhibitor 4SC-205 exhibits antitumor activity and potentiates standard and targeted therapies in primary and metastatic

neuroblastoma models. Clin Transl Med. 2021 Oct;11(10):e533. doi: 10.1002/ctm2.533. PMID: 34709738; PMCID: PMC8516339. (*corresponding authors).

5. Alcon C, Manzano-Muñoz A, Prada E, Mora J, Soriano A, Guillén G, Gallego S, Roma J, Samitier J, Villanueva A, Montero J. Sequential combinations of chemotherapeutic agents with BH3 mimetics to treat rhabdomyosarcoma and avoid resistance. Cell Death Dis. 2020 Aug 15;11(8):634. PMID: 32801295. DOI: 10.1038/s41419-020-02887-y.

6. Carrillo-Reixach J, Torrens L, Simon-Coma M, Royo L, Domingo-Sàbat M, Abril-Fornaguera J, Akers N, Sala M, Ragull S, Arnal M, Villalmanzo M, Cairo S, Villanueva A, Kappler R, Garrido M, Guerra L, Sábado C, Guillén G, Mallo M, Piñeyro D, Vázquez-Vitali M, Kuchuk O, Mateos ME, Ramírez G, López Santamaría M, Mozo Y, Soriano A, Grotzer M, Branchereau S, García de Andoin N, López-Ibor B, López-Almaraz R, Salinas JA, Torres B, Hernández F, Uriz JJ, Fabre M, Blanco J, Paris C, Bajciová V, Laureys G, Masnou H, Clos A, Belendez C, Guettier C, Sumoy L, Planas R, Jordà M, Nonell L, Czauderna P, Morland B, Sia D, Losic B, Annick Buendia M, Sarrias MR, Llovet JM, Armengol C. Epigenetic footprint enables molecular risk stratification of hepatoblastoma with clinical implications. J Hepatol. 2020 Aug;73(2):328-341. doi: 10.1016/j.jhep.2020.03.025. Epub 2020 Mar 30. PMID: 32240714.

7. Zarzosa P, Navarro N, Giralt I, Molist C, Almazán-Moga A, Vidal I, Soriano A, Segura MF, Hladun R, Villanueva A, Gallego S, Roma J. Patient-derived xenografts for childhood solid tumors: a valuable tool to test new drugs and personalize treatments. Clin Transl Oncol. 2017 Jan;19(1):44-50. doi: 10.1007/s12094-016-1557-2. Epub 2016 Oct 7. PMID: 27718156


PAST MEMBERS:


The success of our clinical trials unit has been possible thanks to the pioneering work by Soledad Gallego, MD, PhD. Former Division Head of Pediatric Hematology and Oncology of Vall d’Hebron Hospital and Chair of the Cancer in Childhood and Adolescence Group of VHIR.

Josep Sanchez de Toledo, MD, PhD. Former Division Head of Pediatric Hematology and Oncology of Vall d’Hebron Hospital and Chair of the Cancer in Childhood and Adolescence Group of VHIR.

IP: Lucas Moreno Martín-Retortillo, Aroa Soriano Fernández

Projectes

TACTIC: Explorando soluciones a los retos de salud mediante ciencia disruptiva, terapias avanzadas y medicina de sistemas

IP: Begoña Benito Villabriga
Col·laboradors: Carmen Escudero Iriarte, Laia Ventura i Expósito, Susana Otero Romero, TACTIC: Explorando soluciones a los retos de salud mediante ciencia disruptiva, terapias avanzadas y medicina de sistemas, Ignacio Ferreira González, José Antonio Barrabés Riu, Carlos Nos Llopis, Pablo Velasco Puyó, Jose Fernando Rodríguez Palomares, María Rosario Pérez- Torres Lobato, Sunny Malhotra Sareen, Perez Dueñas, Belen, Jaume Sastre Garriga, Joan López Hellin, Antonia Sambola Ayala, Jordi Rio Izquierdo, Nuria Rivas Gandara, Jordi Perez Rodon, Aroa Soriano Fernández, Manuel Comabella Lopez, Antonio Rodríguez Sinovas, Gisela Teixido Tura, Antonia Pijuan Domenech, Roser Ferrer Costa, Joaquin Seras Franzoso, Carmen Tur Gomez, Maria Cristina Díaz de Heredia Rubio, Laia Yañez Bisbe, Julia German Cortes, Maria Jose Pérez García, Miguel Segura Ginard, Diego Baranda Martínez-Abasca, Cristina Auger Acosta, Neus Bellera Gotarda, Herena Eixarch Ahufinger, M Mar Mañu Pereira, Deborah Pareto Onghena, Lorena Valero Arrese, Aitor Uribarri Gonzalez, Jordi Bañeras Rius, Alex Rovira Cañellas, Mar Tintore Subirana, Bruno García del Blanco, Maria Teresa Salcedo Allende, Marisol Ruiz Meana, Ana Belén Méndez Fernández, Xavier Montalban Gairín, Simon Schwartz Navarro, Anna Llort Sales, Carmen Espejo Ruiz, Raquel Hladun Alvaro, Angels Alcina Mila, Sandra Mancilla Zamora, Zamira Vanessa Diaz Riascos, Ana Zabalza de Torres, Ariadna Boloix Amenós, Marc Miquel Moltó Abad, Javier Inserte Igual, Luciana Midaglia Fernandez, Elizabeth Pando Rau, Gabriela Guillén Burrieza, Cazurro Gutierrez, Ana Laura, Gómez Andrés, David, Alvaro Cobo Calvo, Alvaro Calabuig Goena, Joaquin Castillo Justribo, Lydia Dux-Santoy Hurtado, Lucas Moreno Martín-Retortillo, Andres Miguez Gonzalez, Josep Roma Castanyer, Laura Dos Subirá, Nicolás Miguel Fissolo, Maria Nazarena Pizzi, Tian Tian, Bou Teen, Diana, Fernanda Raquel Da Silva Andrade, Diana Fernandes de Rafael, Andrea Guala
Entitat finançadora: Instituto de Salud Carlos III
Finançament: 2494527.53
Referència: FORT23/00034
Durada: 01/01/2024 - 31/12/2027

Grup de Recerca Emergent (GRE) Childood Cancer & Blood disorders

IP: Lucas Moreno Martín-Retortillo
Col·laboradors: Luís Gros Subias, Raquel Andreu Vilarroig, Andrea Vilaplana Blanes, Pablo Velasco Puyó, Laura Murillo Sanjuán, Maria Isabel Benitez Carabante, Aroa Soriano Fernández, Guillem Pons Barcons, Jose Miguel Lizcano De Vega, Maria Cristina Díaz de Heredia Rubio, María de los Ángeles Rodríguez Sánchez, Uría Oficialdegui, Maria Luz, Maria Jose Pérez García, Miguel Segura Ginard, M Mar Mañu Pereira, Lorena Valero Arrese, Thaïs Murciano Carrillo, Constantino Sábado Álvarez, Anna Llort Sales, Elisabet Megías Roda, Raquel Hladun Alvaro, Ariadna Boloix Amenós, Carlota Aguilera Ordoñez, Adria Molero Valenzuela, Júlia Sansa Girona, Gabriela Guillén Burrieza, Laura Alonso Garcia, Victoria Gutierrez Valle, Idoia Bolinaga Ayala, Josep Roma Castanyer, Sergio Espinosa Gil, Elena Andretta, Claire Diot, Amira Idrizovic
Entitat finançadora: Agència Gestió Ajuts Universitaris i de Recerca
Finançament: 60000
Referència: 2021 SGR 00638
Durada: 01/01/2022 - 30/06/2025

pendent

IP: Aroa Soriano Fernández
Col·laboradors: Judit Álvarez González
Entitat finançadora: Sdad. Española de Hematologia Oncologia Pediatrica
Finançament: 16000
Referència: 2021/CRIS/SEHOP/SORIANO
Durada: 01/07/2023 - 31/12/2023

A phase I trial of ABTL0812 in paediatric patients with advanced cancer including neuroblastoma

IP: Lucas Moreno Martín-Retortillo
Col·laboradors: Soledad Gallego Melcón, Cristina Gamez Cenzano, Aroa Soriano Fernández, Luis Riera Soler, Miguel Segura Ginard, Carlota Aguilera Ordoñez, Sergio Manresa Vera
Entitat finançadora: Instituto de Salud Carlos III
Finançament: 826760.77
Referència: ICI21/00076
Durada: 01/01/2022 - 31/12/2025

Notícies relacionades

L’estudi, que ofereix una guia per al maneig clínic d’aquests pacients, revela que només els menors amb trasplantament recent de cèl·lules mare hematopoètiques o que pateixen altres malalties addicionals tenen un major risc de complicacions per COVID-19.

“Generació d’un banc de models PDX (patient-derived xenografts) ortotòpics quirúrgics en el marc d’un programa de medicina personalitzada en càncer pediàtric” ha estat el treball premiat, del grup de recerca Càncer i Malalties Hematològiques Infantils.

En el Dia Mundial de l’Assaig Clínic, destaquem alguns dels estudis on hem participat que han confirmat l’eficàcia de nous fàrmacs i n’han permès l’aprovació per les agències reguladores.

Professionals relacionats

Victoria Reyes López

Victoria Reyes López

Llegir més
Africa Hontalba Rifa

Africa Hontalba Rifa

Llegir més
Francisco Javier Medel Rebollo

Francisco Javier Medel Rebollo

Farmacologia clínica
Llegir més
Carme Garcia Esquerda

Carme Garcia Esquerda

Llegir més

Subscriu-te als nostres butlletins i forma part de la vida del Campus

El Vall d’Hebron Barcelona Hospital Campus és un parc sanitari de referència mundial on assistència, recerca, docència i innovació es donen la mà.