Herrero, A.B. (Ana B.)

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    Prospective Real-World Gynaecological Cancer Clinical Registry with Associated Biospecimens: A Collaborative Model to Promote Translational Research between GEICO and the Spanish Biobank Network
    (2022) Herrero, A.B. (Ana B.); Recalde, D. (Delia); Gallego-Martínez, A. (Alejandro); Esteban, C. (Carmen); Levin, A. M. (Ana M.); López-Guerrero, J.A. (José Antonio); Churruca, C. (Cristina); Gómez-Raposo, C. (César); Alarcón, J. (Jesús); Mendiola, M. (Marta); González-Martín, A. (Antonio); Marquina, G. (Gloria); Perez-Fidalgo, J.A. (José Alejandro); de Juan, A. (Ana); Torres, A. (Ana); Sánchez-Lorenzo, M. L. (María Luisa); Molina, E. (Elena); Gálvez-Montosa, F. (Fernando); Rubio, M. J. (María Jesús); Romero, I. (Ignacio); Guerra-Alia, E. (Eva)
    Patient registries linked to biorepositories constitute a valuable asset for clinical and translational research in oncology. The Spanish Group of Ovarian Cancer Research (GEICO), in collaboration with the Spanish Biobank Network (RNBB), has developed a multicentre, multistakeholder, prospective virtual clinical registry (VCR) associated with biobanks for the collection of real-world data and biological samples of gynaecological cancer patients. This collaborative project aims to promote research by providing broad access to high-quality clinical data and biospecimens for future research according to the needs of investigators and to increase diagnostic and therapeutic opportunities for gynaecological cancer patients in Spain. The VCR will include the participation of more than 60 Spanish hospitals entering relevant clinical information in harmonised electronic case report forms (eCRFs) in four different cohorts: ovarian, endometrial, cervical, and rare gynaecological cancers (gestational trophoblastic disease). Initial data for the cases included till December 2021 are presented. The model described herein establishes a real-world win-win collaboration between multicentre structures, promoted and supported by GEICO, that will contribute to the success of translational research in gynaecological cancer.
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    Deregulation of DNA double-strand break repair in multiple myeloma: implications for genome stability
    (Public Library of Science, 2015) Herrero, A.B. (Ana B.); Gutierrez, N.C. (Norma C.); San-Miguel, J.F. (Jesús F.)
    Multiple myeloma (MM) is a hematological malignancy characterized by frequent chromosome abnormalities. However, the molecular basis for this genome instability remains unknown. Since both impaired and hyperactive double strand break (DSB) repair pathways can result in DNA rearrangements, we investigated the functionality of DSB repair in MM cells. Repair kinetics of ionizing-radiation (IR)-induced DSBs was similar in MM and normal control lymphoblastoid cell lines, as revealed by the comet assay. However, four out of seven MM cell lines analyzed exhibited a subset of persistent DSBs, marked by γ-H2AX and Rad51 foci that elicited a prolonged G2/M DNA damage checkpoint activation and hypersensitivity to IR, especially in the presence of checkpoint inhibitors. An analysis of the proteins involved in DSB repair in MM cells revealed upregulation of DNA-PKcs, Artemis and XRCC4, that participate in non-homologous end joining (NHEJ), and Rad51, involved in homologous recombination (HR). Accordingly, activity of both NHEJ and HR were elevated in MM cells compared to controls, as determined by in vivo functional assays. Interestingly, levels of proteins involved in a highly mutagenic, translocation-promoting, alternative NHEJ subpathway (Alt-NHEJ) were also increased in all MM cell lines, with the Alt-NHEJ protein DNA ligase IIIα, also overexpressed in several plasma cell samples isolated from MM patients. Overactivation of the Alt-NHEJ pathway was revealed in MM cells by larger deletions and higher sequence microhomology at repair junctions, which were reduced by chemical inhibition of the pathway. Taken together, our results uncover a deregulated DSB repair in MM that might underlie the characteristic genome instability of the disease, and could be therapeutically exploited
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    Rucaparib in recurrent ovarian cancer: real-world experience from the rucaparib early access programme in Spain – A GEICO study
    (2022) Herrero, A.B. (Ana B.); Manso, L. (Luis); Calzas, J. (Julia); Reche, P. (Piedad); Yubero, A. (Alfonso); Barquín, A. (Aranzazu); Salvador, C. (Carmen); Márquez, R. (Raúl); Alarcón, J. (Jesús); Estévez, P. (Purificación); Constenla, M. (Manuel); Gutiérrez, M. (María); Fuentes, J.A. (José Antonio); González-Martín, A. (Antonio); Marquina, G. (Gloria); Gaba, L. (Lydia); Merino, M. (María); Pajares, B. (Bella); Sánchez-Lorenzo, M. L. (María Luisa); Madani, J. (Julia); Casado, V. (Victoria); Taus, A. (Álvaro); Dosil, A. (Alba); Santaballa, A. (Ana)
    Background: Rucaparib is a poly(ADP-ribose) polymerase inhibitor approved in Europe as maintenance therapy for recurrent platinum-sensitive (Pt-S) ovarian cancer (OC). The Rucaparib Access Programme (RAP) was designed to provide early access to rucaparib for the above-mentioned indication, as well as for patients with BRCA-mutated Pt-S or platinum-resistant (Pt-R) OC and no therapeutic alternatives. Methods: In this observational, retrospective study we analysed the efficacy and safety of rucaparib within the RAP in Spain. Hospitals associated with the Spanish Ovarian Cancer Research Group (GEICO) recruited patients with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer treated with rucaparib 600 mg twice daily as maintenance or treatment (Pt-S/Pt-R) in the RAP. Baseline characteristics, efficacy, and safety data were collected. Results: Between July 2020 and February 2021, 51 patients treated in 22 hospitals in the RAP were included in the study. Eighteen patients with a median of 3 (range, 1–6) prior treatment lines received rucaparib as maintenance; median progression-free survival (PFS) for this group was 9.1 months (95% confidence interval [CI], 4.2–11.6 months). Among 33 patients (median 5 [range, 1–9] prior treatment lines) who received rucaparib as treatment, 7 and 26 patients had Pt-S and Pt-R disease, respectively. Median PFS was 10.6 months (95% CI, 2.5 months-not reached) in the Pt-S group and 2.2 months (95% CI, 1.1–3.2 months) in the Pt-R group. Grade ≥ 3 treatment-emergent adverse events were reported in 39% of all patients, the most common being anaemia (12% and 15% in the maintenance and treatment groups, respectively). At data cut-off, 5 patients remained on treatment. Conclusion Efficacy results in these heavily pre-treated patients were similar to those from previous trials. The safety profile of rucaparib in real life was predictable and manageable.