A5039923734- Intraperitoneal and Appendiceal Malignancies
- Hormonal Regulation and Hypertension
- Colorectal Cancer Treatments and Studies
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Adrenal and Paraganglionic Tumors
- PI3K/AKT/mTOR signaling in cancer
- Cancer Genomics and Diagnostics
- Wnt/β-catenin signaling in development and cancer
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer-related gene regulation
- Cancer-related Molecular Pathways
- Science, Research, and Medicine
- FOXO transcription factor regulation
- Cancer Mechanisms and Therapy
- Prostate Cancer Treatment and Research
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- Cell Adhesion Molecules Research
- Melanoma and MAPK Pathways
- Advanced Breast Cancer Therapies
- Liver physiology and pathology
- Neuroendocrine Tumor Research Advances
- Genetic factors in colorectal cancer
- 14-3-3 protein interactions
Vall d'Hebron Institute of Oncology
2011-2025
Centro de Investigación Biomédica en Red de Cáncer
2023-2025
CIBBIM-Nanomedicine
2012-2023
Vall d'Hebron Hospital Universitari
2022-2023
Cells Therapy (Poland)
2014
Barcelona Biomedical Research Park
2013
Molecular Oncology (United States)
2013
Cancer Genomics Centre
2013
Institutul National Victor Babes
2012
Oncogenic mutations in the KRAS/PI3K/AKT pathway are one of most frequent alterations cancer. Although PI3K or AKT inhibitors show promising results clinical trials, drug resistance frequently emerges. We previously revealed Wnt/β-catenin signaling hyperactivation as responsible for such colorectal Here we investigate Wnt-mediated patients treated with trials and evaluate efficacy a new Wnt/tankyrase inhibitor, NVP-TNKS656, to overcome resistance.Colorectal cancer patient-derived sphere...
Aberrant activation of the Wnt/β-catenin pathway is critical for initiation and progression most colon cancers. This provokes accumulation nuclear β-catenin induction its target genes. Apc(min/+) mice are commonly used model cancer. They harbor a mutated Apc allele develop intestinal adenomas carcinomas during first months life. phenotype caused by mutation second consequent in affected cells. Here we describe that vitamin D receptor (VDR) crucial modulator levels cancer vivo. By appropriate...
Dormant or slow-cycling tumor cells can form a residual chemoresistant reservoir responsible for relapse in patients, years after curative surgery and adjuvant therapy. We have adapted the pulse-chase expression of H2BeGFP labeling isolating cancer (SCCCs). SCCCs showed initiation potential enhanced chemoresistance. Cells at this status presented distinctive nongenetic cell-autonomous gene profile shared across different types. identified TET2 epigenetic enzyme as key factor controlling SCCC...
Significance The Notch signaling cascade is deregulated by oncogenic lesions in human cancers and has therefore become an attractive therapeutic target. Inhibitory monoclonal antibodies small-molecule γ-secretase inhibitors have been developed to target the pathway at most proximal point of cascade. Major hurdles application these prevalent dose-limiting toxicities intestine. Here we report identification preclinical validation a small molecule (CB-103) that inhibits level transcription...
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...
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...
Pseudomyxoma peritonei (PMP) is a rare and poorly understood malignant condition characterized by the accumulation of intra-abdominal mucin produced from peritoneal metastases. Currently, cytoreductive surgery remains mainstay treatment but disease recurrence death after relapse frequently occur in patients with PMP. New therapeutic strategies are therefore urgently needed for these patients.
Colon cancer is the second most common cause of death worldwide. Despite advances in development new molecular strategies for stratifying patients with colon cancer, many these do not respond adequately to standard care. While previous studies have focused on prognostic gene expression signatures, exploration predictive signatures inform treatment decisions remains incomplete. In this study, we leveraged public datasets design and experimentally validate a 37-gene signature prognosis...
The detection of correlations between the expression levels or sub-cellular localization different proteins with speci c characteristics human tumors, such as e.g.grade malignancy, may give important hints functional associations.Here we describe method use for relative quanti cation immuno uorescence staining tumor tissue sections, which allows us to compare samples based objective data.With this strategy have ed, instance, amounts nuclear FOXO3a and Beta-Catenin in colon carcinomas.
PI3K pathway activation occurs in concomitance with RAS/BRAF mutations colorectal cancer, limiting the sensitivity to targeted therapies. Several clinical studies are being conducted test tolerability and activity of dual MEK blockade solid tumors.In present study, we explored efficacy cancer preclinical models harboring concomitant ERK pathways. Moreover, investigated if TP53 mutation affects response this therapy.Dual mTORC1/2 resulted synergistic antiproliferative effects cell lines...
Despite the revolution of immunotherapy in cancer treatment, patients eventually progress due to emergence resistance. In this scenario, selection tumor antigen can be decisive success clinical response. T cell bispecific antibodies (TCBs) are engineered molecules that include binding sites receptor and a antigen. Using gastric CEA+/HER2+ MKN45 cells TCBs directed against CEA or HER2, we show mechanism resistance TCB is dependent on Acquired resistant models high-affinity-CEA-targeted...
Tumor relapse is linked to rapid chemoresistance and represents a bottleneck for cancer therapy success. Engagement of reduced proliferation state non-mutational mechanism exploited by cells bypass therapy-induced cell death. Through combining functional pulse-chase experiments in engineered transcriptomic analyses, we identify DPPA3 as master regulator slow-cycling chemoresistant phenotype colorectal (CRC). We find vicious DPPA3-HIF1α feedback loop that downregulates FOXM1 expression via...
<p>BRAF inhibitor suppresses subcutaneous tumor growth in a <i>BRAF</i><sup>V600E</sup> PMP-PDX model. mutant cells from PMP5.1 were subcutaneously implanted mice and treated with vehicle, intraperitoneal cetuximab (20 mg/kg), oral encorafenib or doublet (<i>n</i> = 10–12/group). <b>A,</b> Tumor curve of the overtime. Mean ± SEM is shown. <b>B,</b> Graphs show Western blot quantification pEGFR/EGFR (left) pERK/ERK (right)...
4112 Background: BRAF V600 mt mCRC is an aggressive disease with poor OS under standard chemotherapy. Treatment doublet and triplet targeted combinations, such as inhibitor+ antiEGFR+/- MEK inhibitor, has been shown to improve outcomes. Prognostic factors in this treated population remain be studied. Methods: Prospective international cohort of patients who received or anti-BRAF combinations clinical trials compassionate use. Univariate Cox models for were constructed the strongest...
The analysis of the amounts several proteins, which are found in different sub-cellular compartments, by immuno uorescence can be affected artifacts that need to detected and, if possible, corrected.In case nuclear β-catenin, its detection is usually signal obtained from plasma membrane cells \(which contain most abundant pool beta-catenin).Here we describe an improved method for relative quanti cation β-catenin uorescent staining human colon carcinoma FFPE samples.
Over the last decade, more sophisticated preclinical colorectal cancer (CRC) models have been established using patient-derived cells and 3D tumoroids. Since patient derived tumor organoids can retain characteristics of original tumor, these reliable enable drug screening study resistance mechanisms. However, CRC related death in patients is mostly associated with presence metastatic disease. It therefore essential to evaluate efficacy anti-cancer therapies relevant vivo that truly...
<p>Supplementary Figure 6. Treatment with KRASG12D inhibitor reduces cell viability in mutant PMP-PDXO model a dose dependent manner.</p>
<p>Supplementary Figure 6. Treatment with KRASG12D inhibitor reduces cell viability in mutant PMP-PDXO model a dose dependent manner.</p>