López-Ríos, F. (Fernando)

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2018 - 20203

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    Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study
    (Elsevier BV, 2019) Gonzalez-Larriba, J.L. (José Luis); Plaza, M.L. (María Luz); Rodríguez-Abreu, D. (Delvys); Domine, M. (Manuel); Lozano, M.D. (María Dolores); García-González, J (Jorge); Enguita, A.B. (Ana Belén); Gomez-Roman, J. (Javier); Lázaro-Quintela, M. (Martín); Aguiar, D. (David); Saiz, M. (Mónica); Felip, E. (Enriqueta); Muriel, A. (Alfonso); López-Brea, M. (Marta); Mancheño, N. (Nuria); Arriola, E. (Edurne); Conde, E. (Esther); Garrido, P. (Pilar); Atienza-Cuevas, L. (Lidia); González-Piñeiro, A. (Ana); Jiménez, B. (Beatriz); Gurpide, A. (Alfonso); Martínez-Turrillas, R. (Rebeca); Arriola-Arellano, E. (Esperanza); Esteban-Rodríguez, I. (Isabel); Teixidó, C. (Cristina); Company, A. (Amparo); Aranda, I. (Ignacio); Hernández, S. (Susana); Moran, T. (Teresa); Castro, J. (Javier) de; Camacho, C. (Carmen); Benito, A. (Amparo); Álvarez, R. (Ramiro); Paz-Ares, L. (Luis); Mate, J.L. (Jose Luis); Sansano, I. (Irene); Reguart, N. (Noemi); López-Ríos, F. (Fernando); Artal, Á. (Ángel); Angulo, B. (Bárbara); Juan, O. (Oscar); García, F. (Felip); Abdulkader, I. (Ihab); Salido, M. (Marta); Sanz, J. (Julián); Collazo-Lorduy, A. (Ana); Rojo-Todo, F. (Federico); Insa, A. (Amelia); Pijuan, L. (Lara); Massuti, B. (Bartomeu); Azcona, E. (Eider)
    Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm.
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    Immunotherapy moves to the early-stage setting in non-small cell lung cancer: emerging evidence and the role of biomarkers
    (MDPI AG, 2018) Berraondo, P. (Pedro); Couñago, F. (Felipe); Hernando-Trancho, F. (Florentino); Calvo, V. (Virginia); Mielgo-Rubio, X. (Xabier); Conde, E. (Esther); Martín, M. (Margarita); De-Castro, J. (Javier); López-Ríos, F. (Fernando); Provencio, M. (Mariano); Luna, J. (Javier); Remon, J. (Jordi); Higuera, O. (Oliver); Jarabo, J.R. (José Ramón)
    Despite numerous advances in targeted therapy and immunotherapy in the last decade, lung cancer continues to present the highest mortality rate of all cancers. Targeted therapy based on specific genomic alterations, together with PD-1 and CTLA-4 axis blocking-based immunotherapy, have significantly improved survival in advanced non-small cell lung cancer (NSCLC) and both therapies are now well-established in this clinical setting. However, it is time for immunotherapy to be applied in patients with early-stage disease, which would be an important qualitative leap in the treatment of lung cancer patients with curative intent. Preliminary data from a multitude of studies are highly promising, but therapeutic decision-making should be guided by an understanding of the molecular features of the tumour and host. In the present review, we discuss the most recently published studies and ongoing clinical trials, controversies, future challenges and the role of biomarkers in the selection of best therapeutic options.
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    FGFR1 and FGFR4 oncogenicity depends on n-cadherin and their coexpression may predict FGFR-targeted therapy efficacy
    (2020) Ojeda, L. (Laura); García, S. (Santiago); Vicent, S. (Silvestre); Zugazagoitia, J. (Jon); Quintanal-Villalonga, Á. (Álvaro); Carnero, A. (Amancio); Montuenga-Badia, L.M. (Luis M.); Molina-Pinelo, S. (Sonia); Guruceaga, E. (Elizabeth); Paz-Ares, L. (Luis); Ferrer, I. (Irene); López-Ríos, F. (Fernando); Muñoz-Galván, S. (Sandra); Marrugal, Á. (Ángela); Cirauqui, C. (Cristina)
    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 vivo functional assessments of the oncogenic potential of downregulated/overexpressed genes in isogenic cell lines were performed, as well as inhibitor efficacy tests in vitro and in vivo in patient-derived xenografts (PDXs). mRNA was extracted from FFPE non-small cell lung cancer samples to determine the prognostic potential of the genes under study. Findings: We provide in vitro and in vivo evidence showing that expression of the adhesion molecule N-cadherin is key for the oncogenic role of FGFR1/4 in non-small cell lung cancer. According to this, assessment of the expression of genes in different lung cancer patient cohorts showed that FGFR1 or FGFR4 expression alone showed no prognostic potential, and that only co-expression of FGFR1 and/or FGFR4 with N-cadherin inferred a poorer outcome. Treatment of high-FGFR1 and/or FGFR4-expressing lung cancer cell lines and patient-derived xenografts with selective FGFR inhibitors showed high efficacy, but only in models with high FGFR1/4 and N-cadherin expression. Interpretation: Our data show that the determination of the expression of FGFR1 or FGFR4 alone is not sufficient to predict anti-FGFR therapy efficacy; complementary determination of N-cadherin expression may further optimise patient selection for this therapeutic strategy.