Alba Llop‐Guevara
A5067794408- PARP inhibition in cancer therapy
- Ovarian cancer diagnosis and treatment
- Genetic factors in colorectal cancer
- BRCA gene mutations in cancer
- DNA Repair Mechanisms
- Cancer Genomics and Diagnostics
- Advanced Breast Cancer Therapies
- Radiomics and Machine Learning in Medical Imaging
- Cholangiocarcinoma and Gallbladder Cancer Studies
- CRISPR and Genetic Engineering
- Peptidase Inhibition and Analysis
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Helicobacter pylori-related gastroenterology studies
- Asthma and respiratory diseases
- Colorectal Cancer Treatments and Studies
- IL-33, ST2, and ILC Pathways
- Cancer Research and Treatments
- Prostate Cancer Treatment and Research
- Eosinophilic Esophagitis
- Food Allergy and Anaphylaxis Research
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- Allergic Rhinitis and Sensitization
- Molecular Biology Techniques and Applications
Vall d'Hebron Institute of Oncology
2016-2025
Vall d'Hebron Hospital Universitari
2019-2024
Vall d'Hebron Institut de Recerca
2021-2024
AstraZeneca (Spain)
2024
CIBBIM-Nanomedicine
2018-2023
Centro de Investigación Biomédica en Red
2018
McMaster University Medical Centre
2013-2015
Light Prescriptions Innovators (Spain)
2015
McMaster University
2007-2014
BackgroundBRCA1 and BRCA2 (BRCA1/2)-deficient tumors display impaired homologous recombination repair (HRR) enhanced sensitivity to DNA damaging agents or poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). Their efficacy in germline BRCA1/2 (gBRCA1/2)-mutated metastatic breast cancers has been recently confirmed clinical trials. Numerous mechanisms of PARPi resistance have described, whose relevance gBRCA-mutated cancer is unknown. This highlights the need identify functional biomarkers...
Research Article30 October 2018Open Access Source DataTransparent process A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation Marta Castroviejo-Bermejo Experimental Therapeutics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain Search for more papers by this author Cristina Cruz High Risk and Familial Cancer Department Medical Hospital d'Hebron, Universitat Autònoma de Alba Llop-Guevara Sara Gutiérrez-Enríquez Oncogenetics Mandy Ducy...
•We observed an objective response to olaparib in 18 out of 32 (56%) unselected, primary triple negative breast cancers.•Homologous recombination deficiency (HRD) was determined by targeted DNA sequencing and BRCA1 methylation.•HRD predictive present 16 responders.•HRD also beyond germline BRCA1/2 gPALB2 mutations; 12 14 responders.•Olaparib associated with minor side-effects did not influence subsequent tolerance chemotherapy. BackgroundThe antitumor efficacy PARP inhibitors (PARPi) for...
Abstract PARP inhibitors are approved for treating advanced prostate cancers (APC) with various defective DNA repair genes; however, further studies to clinically qualify predictive biomarkers warranted. Herein we analyzed TOPARP-B phase II clinical trial samples, evaluating whole-exome and low-pass whole-genome sequencing IHC IF assays ATM RAD51 foci (testing homologous recombination function). BRCA1/2 germline somatic pathogenic mutations associated similar benefit from olaparib; greater...
Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, but existence and relative frequency clinical disease are unclear, as is how resistance.
Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, Th2 priming was restored by reconstitution with il4+/+ or il4−/− eosinophils. controlled CD103+ dendritic cell (DC) activation migration intestine to draining lymph nodes, events necessary priming. Eosinophil in vitro vivo led degranulation eosinophil...
Abstract PARP inhibitors (PARPi) are approved drugs for platinum-sensitive, high-grade serous ovarian cancer (HGSOC) and breast, prostate, pancreatic cancers (PaC) harboring genetic alterations impairing homologous recombination repair (HRR). Detection of nuclear RAD51 foci in tumor cells is a marker HRR functionality, we previously established test to detect foci. Here, aimed validate the score cut off compare performance this other deficiency (HRD) detection methods. Laboratory models from...
To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples.
Poly (ADP-ribose) polymerase 1 and 2 (PARP1/2) inhibitors (PARPi) are targeted therapies approved for homologous recombination repair (HRR)-deficient breast, ovarian, pancreatic, prostate cancers. Since inhibition of PARP1 is sufficient to cause synthetic lethality in tumors with deficiency (HRD), selective such as saruparib (AZD5305) being developed. It expected that leads a safer profile facilitates its combination other DNA damage inhibitors. Here, we aimed characterize the antitumor...
Intestinal T helper type 2 (Th2) immunity in food allergy results IgG1 and IgE production, antigen re-exposure elicits responses such as anaphylaxis eosinophilic inflammation. Although interleukin-4 (IL-4) is critically required for allergic sensitization, the source control of IL-4 during initiation Th2 vivo remains unclear. Non-intestinal non-food systems have suggested that natural killer-like (NKT) or γδ T-cell innate lymphocytes can supply to induce polarization. Group lymphoid cells...
Determining the cellular and molecular phenotypes of inflammation in asthma can identify patient populations that may best benefit from targeted therapies. Although elevated IL-6 polymorphisms signalling are associated with lung dysfunction asthma, it remains unknown if levels a specific inflammatory phenotype, how blockade might impact such responses.Patients undergoing exacerbations were phenotyped according to their airway characteristics (normal cell count, eosinophilic, neutrophilic,...
PARP inhibitors (PARPi) induce synthetic lethality in homologous recombination repair (HRR)-deficient tumors and are used to treat breast, ovarian, pancreatic, prostate cancers. Multiple PARPi resistance mechanisms exist, most resulting restoration of HRR protection stalled replication forks. ATR inhibition was highlighted as a unique approach reverse both aspects resistance. Recently, however, PARPi/WEE1 inhibitor (WEE1i) combination demonstrated enhanced antitumor activity associated with...
<p>Supplementary figure 2: Distribution of RAD51 and γH2AX continue values</p>
<p>Supplementary figure 3: Multivariable logistic model to evaluate pCR using sTILs with 30% cut-off</p>
<p>Supplementary figure 1: Immunofluorescence images showing geminin-positive cells with and without RAD51 foci</p>
<div>AbstractPurpose:<p>The randomized GeparOLA trial reported comparable pathologic complete response (pCR) rates with neoadjuvant treatment containing olaparib versus carboplatin. In this study, we evaluate the association between functional homologous recombination deficiency (HRD) by RAD51 foci and pCR potential of improving patient selection combining stromal tumor-infiltrating lymphocytes.</p>Patients Methods:<p>This is a <i>post hoc</i> blinded...
<p>Supplementary figure 4: Disease-free survival according to treatment and RAD51</p>