A5001410842- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Lung Cancer Treatments and Mutations
- Genetic factors in colorectal cancer
- Radiomics and Machine Learning in Medical Imaging
- Melanoma and MAPK Pathways
- Colorectal Cancer Surgical Treatments
- HER2/EGFR in Cancer Research
- Gastric Cancer Management and Outcomes
- Innovative Microfluidic and Catalytic Techniques Innovation
- Synthesis and biological activity
- Peptidase Inhibition and Analysis
- Cancer Treatment and Pharmacology
- Colorectal and Anal Carcinomas
- Hepatocellular Carcinoma Treatment and Prognosis
- Monoclonal and Polyclonal Antibodies Research
- NF-κB Signaling Pathways
- Cutaneous Melanoma Detection and Management
- Pancreatic and Hepatic Oncology Research
- Computational Drug Discovery Methods
- Colorectal Cancer Screening and Detection
- Cancer Mechanisms and Therapy
- Cancer Immunotherapy and Biomarkers
- Synthesis of Tetrazole Derivatives
- Prostate Cancer Treatment and Research
Hospital Del Mar
2015-2025
Centro de Investigación Biomédica en Red de Cáncer
2017-2025
Pompeu Fabra University
2012-2025
HM Hospitales
2019-2024
Hospital del Mar Research Institute
2015-2023
Massachusetts General Hospital
2007-2023
Harvard University
2007-2023
Instituto de Salud Carlos III
2019-2022
Centro de Investigación Biomédica en Red
2022
Municipal Institute for Medical Research
2008-2021
Abstract Activating BRAF kinase mutations arise in ∼7% of all human tumors, and preclinical studies have validated the RAF–mitogen-activated protein/extracellular signal-regulated (ERK) kinase–ERK signaling cascade as a potentially important therapeutic target this setting. Selective RAF inhibitors are currently undergoing clinical development, based on experience with other kinase-targeted therapeutics, it is expected that responses to these agents, if observed, will lead eventual emergence...
•Validated and sensitive ctDNA assays can be used to genotype advanced cancers select patients for targeted therapies.•Initial genotyping with should considered when rapid results are needed, tissue is unavailable.•ctDNA assay limited by false-negative results, lower sensitivity fusion events copy number changes.•Use of detect molecular residual disease not recommended, due lack evidence its clinical utility. Circulating tumour DNA (ctDNA) conducted on plasma rapidly developing a strong base...
Kinase inhibitors constitute an important new class of cancer drugs, whose selective efficacy is largely determined by underlying tumor cell genetics. We established a high-throughput platform to profile 500 lines derived from diverse epithelial cancers for sensitivity 14 kinase inhibitors. Most were ineffective against unselected but exhibited dramatic killing small nonoverlapping subsets. Cells with exquisite EGFR, HER2, MET, or BRAF marked activating mutations amplification the drug...
BackgroundRAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination based on tumor tissue, however, genotyping of circulating (ct)DNA offers clear advantages as a minimally invasive method that represents heterogeneity. Our study aims to evaluate the use ctDNA an alternative determining baseline RAS status and subsequent monitoring mutations during component routine clinical practice.Patients methodsRAS mutational plasma was...
Abstract Purpose: Patients with colorectal cancer who respond to the anti-EGFR antibody cetuximab often develop resistance within several months of initiating therapy. To design new lines treatment, molecular landscape resistant tumors must be ascertained. We investigated role mutations in EGFR signaling axis on acquisition patients and cellular models. Experimental Design: Tissue samples were obtained from 37 became refractory cetuximab. Colorectal cells sensitive treated until derivatives...
PURPOSE To determine the safety and preliminary efficacy of selective combination targeted therapy for BRAF V600E–mutant metastatic colorectal cancer (mCRC) in lead-in phase open-label, randomized, three-arm, III BEACON Colorectal Cancer trial ( ClinicalTrials.gov identifier: NCT02928224; European Union Clinical Trials Register EudraCT2015-005805-35). PATIENTS AND METHODS Before initiation randomized portion trial, 30 patients with mCRC who had experienced treatment failure one or two prior...
Blockade of the epidermal growth factor receptor (EGFR) with monoclonal antibodies cetuximab or panitumumab is effective in a subset colorectal cancers (CRCs), but emergence resistance limits efficacy these therapeutic agents. At relapse, majority patients develop RAS mutations, while acquires EGFR extracellular domain (ECD) mutations. Here we find that who experience greater and longer responses to blockade preferentially ECD mutations emerge more frequently smaller tumour shrinkage shorter...
Circulating tumor DNA (ctDNA) is a potential source for genome analysis. We explored the concordance between mutational status of RAS in tissue and ctDNA metastatic colorectal cancer (mCRC) patients to establish eligibility anti-epidermal growth factor receptor (EGFR) therapy.A prospective-retrospective cohort study was carried out. Tumor from 146 mCRC tested with standard care (SoC) PCR techniques, Digital (BEAMing) used both plasma tissue.ctDNA BEAMing testing showed 89.7% agreement SoC...
Abstract A substantial proportion of cancer patients do not benefit from platinum-based chemotherapy (CT) due to the emergence drug resistance. Here, we apply elemental imaging mapping CT biodistribution after therapy in residual colorectal and achieve a comprehensive analysis genetic program induced by oxaliplatin-based tumor microenvironment. We show that oxaliplatin is largely retained cancer-associated fibroblasts (CAFs) long time treatment ceased. determine accumulation CAFs intensifies...
Previous studies have highlighted the importance of an appropriate human epidermal growth factor receptor 2 (HER2) evaluation for proper identification patients eligible treatment with anti-HER2 targeted therapies. Today, relationship remains unclear between level HER2 amplification and outcome HER2-positive gastric cancer treated first-line chemotherapy trastuzumab. The aim this study was to determine whether gene determined by HER2/CEP17 ratio copy number could significantly predict some...
<h3>Importance</h3> Acquired resistance to anti-EGFR therapy (epidermal growth factor receptor) is frequently due to<i>RAS</i>and<i>EGFR</i>extracellular domain (ECD) mutations in metastatic colorectal cancer (mCRC). Some anti-EGFR–refractory patients retain tumor EGFR dependency potentially targetable by agents such as Sym004, which a mixture of 2 nonoverlapping monoclonal antibodies targeting EGFR. <h3>Objective</h3> To determine if continuous blockade Sym004 has survival benefit....
An oligoclonal antibody overcomes drug resistance in colorectal cancers with EGFR mutations.
Total neoadjuvant treatment (TNT) is a valid strategy for patients with high-risk locally advanced rectal cancer (LARC). Biomarkers of response to TNT are an unmet clinical need. We aimed determine the value circulating tumor DNA (ctDNA) predict response, recurrence, and survival in LARC treated TNT.The GEMCAD 1402 was phase II randomized, multicentric trial that randomized 180 modified schedule fluorouracil, leucovorin, oxaliplatin (mFOLFOX6) +/- aflibercept, followed by chemoradiation...
Detection of circulating tumor DNA (ctDNA) is a minimally invasive and convenient blood-based screening strategy that may increase effectiveness colorectal cancer (CRC) screening.A novel multimodal ctDNA-based blood assay integrates genomics, epigenomics fragmentomics, as well proteomics in refined version, was tested samples from two cohorts: (i) consecutive fecal immunochemical test (FIT)-positive individuals the CRC Barcelona stool-based program; (ii) patients diagnosed with CRC. Primary...
Abstract Purpose: To investigate whether nuclear factor κB (NF-κB)/interleukin 6 (IL-6) was linked to docetaxel response in human prostate cancer cell lines, and inhibition of NF-κB sensitized tumor cells docetaxel. We also aimed correlate IL-6 (as a surrogate marker NF-κB) hormone-independent (HIPC) patients. Experimental Design: Hormone-dependent (LNCaP) (PC-3 DU-145) lines were exposed alone or combined with the inhibitor PS-1145 (an IκB kinase-2). Effects dose, exposure time, schedule...
Liquid biopsy offers a minimally invasive alternative to tissue-based evaluation of mutational status in cancer. The goal the present study was evaluate aggregate performance OncoBEAM RAS mutation analysis plasma colorectal cancer (CRC) patients at 10 hospital laboratories Spain where this technology is routinely implemented.Circulating cell-free DNA from examined for mutations using platform each laboratory. Results were then compared those obtained extracted tumour tissue same patient.The...
Phosphorylated IKKα(p45) is a nuclear active form of the IKKα kinase that induced by MAP kinases BRAF and TAK1 promotes tumor growth independent canonical NF-κB signaling. Insights into sources activation its downstream substrates in nucleus remain to be defined. Here, we discover rapidly activated DNA damage ATM-ATR, but dependent on BRAF-TAK1-p38-MAPK, required for robust ATM efficient repair. Abolishing or activity attenuates ATM, Chk1, MDC1, Kap1, 53BP1 phosphorylation, compromises RIF1...
Approved anti-EGFR antibodies cetuximab and panitumumab provide significant clinical benefit in patients with metastatic colorectal cancer (MCRC). However, ultimately develop disease progression, often driven by acquisition of mutations the extracellular domain (ECD) EGFR. Sym004 is a novel 1:1 mixture two nonoverlapping mAbs that recently showed promising activity phase I trial MCRC. Our aim was to determine efficacy circumvent resistance EGFR ECD mutations.Functional studies were performed...
Abstract Current therapy against colorectal cancer (CRC) is based on DNA-damaging agents that remain ineffective in a proportion of patients. Whether and how non-curative DNA damage-based treatment affects tumor cell behavior patient outcome primarily unstudied. Using CRC patient-derived organoids (PDO)s, we show sublethal doses chemotherapy (CT) does not select previously resistant populations but induces quiescent state specifically to TP53 wildtype (WT) cells, which linked the acquisition...