A5009397099- Lung Cancer Treatments and Mutations
- Cancer, Hypoxia, and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Chronic Lymphocytic Leukemia Research
- Cancer Treatment and Pharmacology
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Medical Imaging Techniques and Applications
- HER2/EGFR in Cancer Research
- Advanced Breast Cancer Therapies
- Epigenetics and DNA Methylation
- Cancer Research and Treatments
- Radiopharmaceutical Chemistry and Applications
- Cancer Immunotherapy and Biomarkers
- Breast Cancer Treatment Studies
- 3D Printing in Biomedical Research
- Cellular Mechanics and Interactions
- Cancer, Lipids, and Metabolism
- PARP inhibition in cancer therapy
- Ovarian cancer diagnosis and treatment
- Angiogenesis and VEGF in Cancer
- RNA modifications and cancer
- Radiomics and Machine Learning in Medical Imaging
- Fibroblast Growth Factor Research
- Cancer-related Molecular Pathways
Spanish National Cancer Research Centre
2015-2025
Centro de Investigación del Cáncer
2014-2025
Cancer Research Center
2013-2025
Hospital Universitario de Fuenlabrada
2013-2025
Cancer Clinic
2023-2025
Centro Nacional de Investigaciones Científicas
2024
Australia New Zealand Gynaecological Oncology Group
2024
Swansea University
2017-2024
Hospital Universitario Quirónsalud Madrid
2017-2023
Roche (Spain)
2006-2023
While recent innovations in spatial biology have driven new insights into how tissue organization is altered disease, interpreting these datasets a generalized and scalable fashion remains challenge. Computational workflows for discovering condition-specific differences typically rely on pairwise comparisons or unsupervised clustering. In many cases, approaches are computationally expensive, lack statistical rigor, insensitive to low-prevalence cellular niches that nevertheless highly...
Next Generation Sequencing (NGS) panels are increasingly used in advanced patients with cancer to guide therapy. There is, however, controversy about when should these be used, and their impact on the clinical course.In an observational study of 139 having NGS test [from January 1st, 2017 December 30th, 2020, two hospitals (Hospital Universitario de La Princesa Hospital Quironsalud Madrid) from Spain], we evaluated whether course (progression-free survival, PFS) was influenced by drug-based...
Purpose Cisplatin kills tumor cells through DNA cross linking. Alterations in the function of repair genes may affect proficiency and influence cancer patients' response to cisplatin. We studied whether single nucleotide polymorphisms (SNPs) predict cisplatin or prognosis patients with squamous cell carcinoma head neck (SCCHN). Methods A polymerase chain reaction–restriction fragment length polymorphism (RFLP) approach was used determine frequency SNPs: XPD-Asp312Asn, XPD-Lys751Gln,...
Proteins containing a caveolin-binding domain (CBD), such as the Rho-GTPases, can interact with caveolin-1 (Cav1) through its caveolin scaffold domain. Rho-GTPases are important regulators of p130Cas, which is crucial for both normal cell migration and Src kinase-mediated metastasis cancer cells. However, although (particularly RhoC) Cav1 have been linked to progression metastasis, underlying molecular mechanisms largely unknown. To investigate function Cav1–Rho-GTPase interaction in we...
Chemokines are relevant molecules in shaping the tumor microenvironment, although their contributions to tumorigenesis not fully understood. We studied influence of chemokine CX3CL1/fractalkine de novo breast cancer formation using HER2/neu transgenic mice. CX3CL1 expression was downmodulated tumors, yet, paradoxically, adenovirus-mediated milieu enhanced mammary numbers a dose-dependent manner. Increased multiplicity consequence CX3CL1-induced metastatic dissemination primary tumor, induced...
PP2A is a major tumor suppressor whose inactivation frequently found in wide spectrum of human tumors. In particular, deletion or epigenetic silencing genes encoding the B55 family regulatory subunits common feature breast cancer cells. A key player regulation PP2A/B55 phosphatase complexes cell cycle kinase MASTL (also known as Greatwall). During division, inhibition PP2A-B55 by required to maintain mitotic state, whereas and reactivation for exit. Despite its critical role progression...
Abstract Tumors are complex tissues composed of transformed epithelial cells as well cancer-activated fibroblasts (CAF) that facilitate tumor cell invasion. We show here CAFs and other mesenchymal rely much more on glutamine than cells; consequently, they sensitive to inhibition glutaminase. Glutamine dependence drove CAF migration toward this amino acid when cultured in low conditions. also invaded a Matrigel matrix following concentration gradient enhanced the invasion both were...
Upregulation of fatty acid synthase (FASN) is a common event in cancer, although its mechanistic and potential therapeutic roles are not completely understood. In this study, we establish key role FASN during transformation. required for eliciting the anaplerotic shift Krebs cycle observed cancer cells. However, main to consume acetyl-CoA, which unlocks isocitrate dehydrogenase (IDH)-dependent reductive carboxylation, producing power necessary quench reactive oxygen species (ROS) originated...
Abstract Triple-negative breast cancer (TNBC) lacks prognostic and predictive markers. Here, we use high-throughput phosphoproteomics to build a functional TNBC taxonomy. A cluster of 159 phosphosites is upregulated in relapsed cases training set ( n = 34 patients), with 11 hyperactive kinases accounting for this phosphoprofile. mass-spectrometry-to-immunohistochemistry translation step, assessing 2 independent validation sets, reveals 6 preserved value. The split the into two patterns: one...
Abstract Background FGFR1 amplification, but not overexpression, has been related to adverse prognosis in hormone-positive breast cancer (HRPBC). Whether overexpression and amplification are correlated, what is their distribution among luminal A or B HRPBC, if there a potential different prognostic role for currently unknown features. The of inhibitors HRPBC also unclear. Methods (FISH) (RNAscope) were investigated N = 251 patients cohort the METABRIC cohort; effects on survival...
Abstract Purpose: To characterize safety and tolerability of the selective PI3Kβ inhibitor AZD8186, identify a recommended phase II dose (RP2D), assess preliminary efficacy in combination with abiraterone acetate or vistusertib. Patients Methods: This I open-label study included patients advanced solid tumors, particularly prostate cancer, triple-negative breast squamous non–small cell lung cancer. The comprised four arms: (i) AZD8186 monotherapy finding; (ii) expansion; (iii)...
B cell activation factor of the TNF family (BAFF) activates noncanonical nuclear κB (NF-κB) heterodimers that promote survival. We show although MALT1 is largely dispensable for canonical NF-κB signaling downstream receptor, absence results in impaired BAFF-induced phosphorylation NF-κB2 (p100), p100 degradation, and RelB translocation B220+ cells. This corresponds with survival MALT1−/− marginal zone (MZ) but not follicular cells response to BAFF stimulation vitro. MZ also express higher...
Epigenetic clocks have been widely used to estimate biological age across various tissues, but their accuracy in breast tissue remains suboptimal. Pan-tissue models such as Horvath's and Hannum's clocks, perform poorly predicting chronological tissue, underscoring the need for a tissue-specific approach. In this study, we introduce Breast Tissue-specific Clock (BTEC), developed using DNA methylation data from 553 healthy samples seven different studies. BTEC significantly outperformed...
<title>Abstract</title> Epigenetic clocks have been widely used to estimate biological age across various tissues, but their accuracy in breast tissue remains suboptimal. Pan-tissue models such as Horvath’s and Hannum’s clocks, perform poorly predicting chronological tissue, underscoring the need for a tissue-specific approach. In this study, we introduce Breast Tissue-specific Clock (BTEC), developed using DNA methylation data from 553 healthy samples seven different studies. BTEC...
There is active crosstalk between tumor cells and the microenvironment during metastatic progression, a process that significantly affected by obesity, particularly in breast cancer. Here we analyze impact of high fat diet (HFD) on metastasis, focusing role platelets formation premetastatic niches (PMNs). We find HFD provokes pre-activation endothelial cells, promoting PMNs lung. These are characterized increased vascular leakiness, platelet activation overexpression fibronectin both cells....
Background: Rationalization of antiangiogenics requires biomarkers. Vascular re‐normalization is one widely accepted mechanism action for this drug class. The interstitium tumors with abnormal vasculature hypoxic. We sought to track vascular normalization 18F‐misonidazole ([18F]‐FMISO, a probe that detects hypoxia) PET, in response window‐of‐opportunity (WoO) treatment the antiangiogenic dovitinib. Methods: Two patient‐derived pancreas xenografts (PDXs; Panc215 and Panc286) spontaneous...
Inhibitors of the mechanistic target rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis response inhibition. This feature driven by EVI1 SOX9. functionally cooperates with positively regulates SOX9, promotes...
Purpose: We previously detected promising efficacy of neoadjuvant nintedanib (a multityrosine kinase inhibitor, TKI) in early HER2-negative breast cancer. In a preclinical study, we monitored stromal hypoxia with 18F-fluoromisonidazole-positron emission tomography (18F-FMISO-PET); found that reoxygenation tumors (or lack it) during window-of-opportunity (WoO) treatment TKIs correlated the benefit from TKI-plus-chemotherapy combinations. studied predictive role 18F-FMISO-PET for TKI setting...
We previously demonstrated that mitochondrial inhibitors' efficacy was restricted to a metabolic context in which respiration the predominant energy source, situation achievable by inducing vascular normalization/hypoxia correction with antiangiogenics. Vascular normalization can be tracked 2[18F]fluoro-2-deoxy-d-glucose (FDG)-PET. tested of inhibitor ME-344 or placebo added bevacizumab early breast cancer.Treatment-naïve HER2-negative patients T > 1 cm (any N) underwent breast-centered...
Despite strong preclinical data, the therapeutic benefit of RANKL inhibitor, denosumab, in breast cancer patients, beyond bone, is unclear. Aiming to select patients who may from we hereby analyzed RANK and protein expression more than 2,000 tumors (777 estrogen receptor-negative, ER