A5020391246- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- Colorectal Cancer Treatments and Studies
- Protease and Inhibitor Mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Advanced Breast Cancer Therapies
- Cancer Immunotherapy and Biomarkers
- Economic Theory and Policy
- Peptidase Inhibition and Analysis
- Genetic factors in colorectal cancer
- Cancer, Hypoxia, and Metabolism
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Cancer Mechanisms and Therapy
- Cancer, Stress, Anesthesia, and Immune Response
- Advanced Biosensing Techniques and Applications
- Breast Cancer Treatment Studies
- Renal cell carcinoma treatment
- Breast Lesions and Carcinomas
- Cancer-related gene regulation
- Gastric Cancer Management and Outcomes
Bellvitge University Hospital
2024
Vall d'Hebron Institute of Oncology
2014-2023
Molecular Oncology (United States)
2013-2023
Vall d'Hebron Hospital Universitari
2008-2023
University of Michigan–Ann Arbor
2022
National Health Service
2018
Queen's University Belfast
2018
Universitat Autònoma de Barcelona
2010-2017
Hebron University
2010-2015
Vall d'Hebron Institut de Recerca
2011-2015
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...
Clinical benefits from trastuzumab and other anti-HER2 therapies in patients with HER2 amplified breast cancer remain limited by primary or acquired resistance. To identify potential mechanisms of resistance, we established trastuzumab-resistant cells chronic exposure to treatment. Genomewide copy-number variation analyses the resistant compared parental revealed a focal amplification genomic DNA containing cyclin E gene. In cohort 34 + treated trastuzumab-based therapy, found that...
We investigated whether mutations in the gene encoding phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) correlates with response to neoadjuvant human epidermal growth factor receptor 2 (HER2) -targeted therapies patients breast cancer.Baseline tissue biopsies were available from HER2-positive early cancer who enrolled onto Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial (NeoALTTO). Activating PIK3CA identified using mass spectrometry-based...
Cell signaling pathways include a complex myriad of interconnected factors from the membrane to nucleus, such as erbB family receptors and phosphoinositide-3-kinase/Akt/mTOR Ras-Raf-ERK cascades, which drive proliferative signals, promote survival, regulate protein synthesis.
A subgroup of human epidermal growth factor receptor 2 (HER2)-overexpressing breast tumors coexpresses p95HER2, a truncated HER2 that retains highly functional kinase domain but lacks the extracellular and results in intrinsic trastuzumab resistance. We hypothesized lapatinib, tyrosine inhibitor, would be active these tumors. have studied correlation between p95HER2 expression response to both preclinical models clinical setting.Two different animal were used for studies. Expression was...
Accumulating evidence has identified Fusobacterium as an important pathogenic gut bacterium associated with colorectal cancer. Nevertheless, only limited data exist about the role of this in locally advanced rectal cancer (LARC). In study, we quantified nucleatum untreated and post-neoadjuvant chemoradiotherapy (nCRT) samples from LARC patients investigated its association therapy response survival.
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...
Metastatic colorectal cancer (mCRC) patients tend to have modest benefits from molecularly driven therapeutics. Patient-derived tumor organoids (PDTOs) represent an unmatched model elucidate resistance therapy, due their high capacity resemble characteristics.We used viable tissue two cohorts of with mCRC, naïve or refractory treatment, respectively, for generating PDTOs. The derived models were subjected a 6-day drug screening assay (DSA) comprehensive pipeline chemotherapy and targeted...
Abstract Purpose: Expression of p95HER2 has been associated with resistance to trastuzumab-based therapy in patients metastatic breast cancer. Conversely, high levels HER2 have linked increased clinical benefit from anti-HER2 therapy. In this work, we aimed investigate whether the and can predict response Experimental Design: We measured by VeraTag HERmark, respectively, primary tumors enrolled neoadjuvant phase III study NeoALTTO correlated these variables pathologic complete (pCR)...
Current methods to determine HER2 (human epidermal growth factor receptor 2) status are affected by reproducibility issues and do not reliably predict benefit from anti-HER2 therapy. Quantitative measurement of may more accurately identify breast cancer (BC) patients who will respond treatments.Using selected reaction monitoring mass spectrometry (SRM-MS), we quantified protein levels in formalin-fixed, paraffin-embedded (FFPE) tissue samples that had been classified as 0, 1+, 2+ or 3+...
Within the aim of advancing precision oncology, we have generated a collection patient-derived xenografts (PDX) characterized at molecular level, and preclinical model colon cancer metastasis to evaluate drug-response tumor progression.We derived cells from 32 primary colorectal carcinomas eight liver metastases PDX annotated for their clinical data, gene expression, mutational, histopathological traits. Six models were injected orthotopically into cecum wall NOD-SCID mice in order...
Transcriptomic profiling of colorectal cancer (CRC) has led to identification four consensus molecular subtypes (CMS1-4), which have prognostic value in stage II/III disease. More recently, the Colorectal Cancer Intrinsic Subtypes (CRIS) classification system helped define biology specific epithelial component tumors. However, clinical these classifications predicting response standard-of-care adjuvant chemotherapy remains unknown.Using samples from 4 European sites, we assembled a novel CRC...
Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch® system. Given low CTC counts non-metastatic cancer, it is important to evaluate inter-reader agreement. images (N = 272) of either CTCs or white blood artifacts from 109 (M0) and 22 metastatic (M1) patients reported studies were sent readers 15 academic laboratories 8 two Veridex laboratories. Each image was scored as No vs HER2- HER2+. The summarized a Consensus (VC) compare each reader using % agreement...
Hsp90 facilitates the maturation and stability of numerous oncoproteins, including HER2. The aim this study was to assess antitumor activity inhibitor IPI-504 in trastuzumab-resistant, HER2-overexpressing breast cancer cells. Therapy with trastuzumab, IPI-504, combination trastuzumab evaluated trastuzumab-sensitive trastuzumab-resistant Inhibition protein targets, cell proliferation, tumor growth assessed vitro xenograft models. inhibited proliferation both Administration markedly reduced...
Immunotherapy has transformed advanced non-small cell lung cancer (NSCLC) treatment strategies and led to unprecedented long-lasting responses in some patients. However, the molecular determinants driving these long-term remain elusive. To address this issue, we performed an integrative analysis of genomic transcriptomic features immune checkpoint inhibitors (ICIs)-associated responders. We assembled a cohort 47 patients with NSCLC receiving ICIs that was enriched responders [>18 months...
Immunotherapy is effective, but current biomarkers for patient selection have proven modest sensitivity. Here, we developed VIGex, an optimized gene signature based on the expression level of 12 genes involved in immune response with RNA sequencing.We implemented VIGex using nCounter platform (Nanostring) a large clinical cohort encompassing 909 tumor samples across 45 types. was as continuous variable, cutoffs selected to detect three main categories (hot, intermediate-cold and cold)...
Inhibition of the activated epidermal growth factor receptor (EGFR) with either enzymatic kinase inhibitors or anti-EGFR antibodies such as cetuximab, is an effective modality treatment for multiple human cancers. Enzymatic EGFR are lung adenocarcinomas somatic domain mutations while, paradoxically, more in colon and head neck cancers where occur less frequently. In colorectal cancer, routinely used second-line therapy KRAS wild-type tumors. However, detailed mechanisms genomic predictors...
FGFR1 amplification (FGFR1amp) is recurrent in metastatic breast cancer (MBC) and associated with resistance to endocrine therapy CDK4/6 inhibitors (CDK4/6is). Multi-tyrosine kinase (MTKIs) selective pan-FGFR (FGFRis) are being developed for FGFR1amp cancer. High-level FGFR protein expression by IHC have identified responders FGFRis or MTKIs, respectively.Here, we used preclinical models patient samples identify predictive biomarkers these drugs. We evaluated the antitumor activity of an...