226 results match your criteria: "Candiolo Cancer Institute-FPO- IRCCS[Affiliation]"
Background: The NEDD8 conjugation pathway modulates the ubiquitination and activity of a wide range of intracellular proteins, and its blockade by pevonedistat is emerging as a promising therapeutic approach in various cancer settings. However, systematic characterization of pevonedistat efficacy in specific tumor types and definition of response predictors are still missing.
Methods: We investigated in vitro sensitivity to pevonedistat in 122 colorectal cancer (CRC) cell lines by an ATP-based proliferation assay and evaluated apoptosis and DNA content by flow cytometry.
Expert Opin Pharmacother
November 2016
a Investigative Clinical Oncology (INCO) , Candiolo Cancer Institute-FPO- IRCCS, Turin , Italy.
Endocrine therapy is the mainstay of treatment for a substantial proportion of hormone receptor positive (HR+) breast cancer (BC). Indeed, patients with metastatic disease not immediately life threatening may experience long disease control across several lines of endocrine therapy. The major limitation of this therapeutic approach is primary or acquired resistance.
View Article and Find Full Text PDFOncotarget
October 2016
Department of Oncology, University and General Hospital, Udine, Italy.
HER-2 (ErbB-2, c-erbB2 or Her2/neu), a member of the HER-family, is directly involved in the pathogenesis and progression of several human cancers; as such, it is also often considered as a poor prognostic factor. Following the revolutionary impact of anti-HER-2 therapy in breast cancer patients, the role of HER-2 and its blockade has also been extensively evaluated in other tumor types, including gastric and colorectal adenocarcinoma. The aims of this review are to recall the important results achieved with the use of HER-2 inhibitors in both gastric and colorectal cancer, and to discuss on the updates available on the role of HER-2 as prognostic and predictive factor in these malignancies.
View Article and Find Full Text PDFInt J Mol Sci
July 2016
Candiolo Cancer Institute-FPO-IRCCS, Candiolo, Turin 10060, Italy.
Epithelial ovarian cancer (EOC) is the leading cause of death for gynecological cancer. The standard treatment for advanced stage is the combination of optimal debulking surgery and platinum-based chemotherapy. Nevertheless, recurrence is frequent (around 70%) and prognosis is globally poor.
View Article and Find Full Text PDFMol Cancer Res
June 2016
Molecular Biotechnology Center (MBC), University of Torino, Torino, Italy. Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy. Center for Molecular Systems Biology, University of Torino, Torino, Italy.
Unlabelled: Malignant melanoma is the most aggressive form of skin cancer; therefore, it is crucial to disclose its underlying molecular mechanisms. MicroRNAs (miRNAs) are small endogenous noncoding RNAs able to posttranscriptionally downregulate the expression of direct target genes. Using a melanoma progression model, miR-146a was identified as a key double-acting player in melanoma malignancy.
View Article and Find Full Text PDFJ Ovarian Res
May 2016
Candiolo Cancer Institute-FPO- IRCCS, Candiolo, Turin, Italy.
The standard front-line therapy for epithelial ovarian cancer (EOC) is combination of debulking surgery and platinum-based chemotherapy. Nevertheless, the majority of patients experience disease recurrence. Although extensive efforts to find new therapeutic options, cancer cells invariably develop drug resistance and disease progression.
View Article and Find Full Text PDFJ Transl Med
May 2016
Department of Oncology, University of Torino, Turin, Italy.
Background: Angiogenesis inhibition is a promising approach for treating metastatic colorectal cancer (mCRC). Recent evidences support the seemingly counterintuitive ability of certain antiangiogenic drugs to promote normalization of residual tumor vessels with important clinical implications. Lenalidomide is an oral drug with immune-modulatory and anti-angiogenic activity against selected hematologic malignancies but as yet little is known regarding its effectiveness for solid tumors.
View Article and Find Full Text PDFBMC Biol
January 2016
Department of Oncology, University of Torino Medical School, 10060, Candiolo, Torino, Italy.
Background: Tankyrases are poly(adenosine diphosphate)-ribose polymerases that contribute to biological processes as diverse as modulation of Wnt signaling, telomere maintenance, vesicle trafficking, and microtubule-dependent spindle pole assembly during mitosis. At interphase, polarized reshaping of the microtubule network fosters oriented cell migration. This is attained by association of adenomatous polyposis coli with the plus end of microtubules at the cortex of cell membrane protrusions and microtubule-based centrosome reorientation towards the migrating front.
View Article and Find Full Text PDFExpert Opin Biol Ther
July 2016
a Department of Oncology , University of Turin, Turin , Italy.
Genetic engineering of T lymphocytes is an appealing strategy to confer and enhance new antitumor specificities to generate effective anticancer cell products for adoptive immunotherapy. The two main approaches are based either on transgenic tumor-antigen specific T cell receptors (TCR) or chimeric antigen receptors (CAR). Initial clinical trials reported important results against selected diseases, along with relevant warnings.
View Article and Find Full Text PDFSci Rep
October 2015
Quantitative Life Sciences Unit, The Abdus Salam Center for Theoretical Physics (ICTP), Strada Costiera 11, I-34151 Trieste, Italy.
One of the most important steps in tumor progression involves the transformation from a differentiated epithelial phenotype to an aggressive, highly motile phenotype, where tumor cells invade neighboring tissues. Invasion can occur either by isolated mesenchymal cells or by aggregates that migrate collectively and do not lose completely the epithelial phenotype. Here, we show that, in a three-dimensional cancer cell culture, collective migration of cells eventually leads to aggregation in large clusters.
View Article and Find Full Text PDFImmunotherapy
August 2016
Department of Oncology, University of Torino, Turin, Italy.
Cytokine-induced killer (CIK) cells are ex vivo expanded T lymphocytes endowed with potent MHC-independent antitumor activity. CIK cells are emerging as promising therapeutic approach in the field of cancer adoptive immunotherapy, with biologic features favoring their transferability into clinical applications. Aim of this review is to present the biologic characteristic of CIK cells, discussing the main preclinical findings and initial clinical applications in the field of solid tumors.
View Article and Find Full Text PDFClin Cancer Res
December 2015
Department of Oncology, University of Turin Medical School, Turin, Italy. Laboratory of Translational Cancer Medicine, Candiolo Cancer Institute-FPO IRCCS, Turin, Italy.
Purpose: Preclinical studies in HER2-amplified gastrointestinal cancer models have shown that cotargeting HER2 with a monoclonal antibody and a small molecule is superior to monotherapy with either inhibitor, but the underlying cooperative mechanisms remain unexplored. We investigated the molecular underpinnings of this synergy to identify key vulnerabilities susceptible to alternative therapeutic opportunities.
Experimental Design: The phosphorylation/activation of HER2, HER3, EGFR (HER receptors), and downstream transducers was evaluated in HER2-overexpressing colorectal and gastric cancer cell lines by Western blotting and/or multiplex phosphoproteomics.
Clin Cancer Res
December 2015
Experimental Therapeutics Laboratory, Vall d'Hebron Institute of Oncology (VHIO), 08035-Barcelona, Spain.
Purpose: PI3K pathway activation occurs in concomitance with RAS/BRAF mutations in colorectal cancer, limiting the sensitivity to targeted therapies. Several clinical studies are being conducted to test the tolerability and clinical activity of dual MEK and PI3K pathway blockade in solid tumors.
Experimental Design: In the present study, we explored the efficacy of dual pathway blockade in colorectal cancer preclinical models harboring concomitant activation of the ERK and PI3K pathways.
Cancer Discov
August 2015
Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
Unlabelled: The Cancer Genome Atlas project identified HER2 somatic mutations and gene amplification in 7% of patients with colorectal cancer. Introduction of the HER2 mutations S310F, L755S, V777L, V842I, and L866M into colon epithelial cells increased signaling pathways and anchorage-independent cell growth, indicating that they are activating mutations. Introduction of these HER2 activating mutations into colorectal cancer cell lines produced resistance to cetuximab and panitumumab by sustaining MAPK phosphorylation.
View Article and Find Full Text PDFBiochim Biophys Acta
December 2015
Candiolo Cancer Institute-FPO IRCCS, Candiolo 10060, Italy; Department of Oncology, University of Torino, Torino 10043, Italy; Center for Molecular Systems Biology, University of Torino, 10124 Torino, Italy. Electronic address:
The ability of cells to migrate is essential for different physiological processes including embryonic development, angiogenesis, tissue repair and immune response. In the context of cancer such abilities acquire dramatic implications, as they are exploited by tumor cells to invade neighboring or distant healthy tissues. 3-Phosphoinositide dependent protein kinase-1 (PDK1 or PDPK1) is an ancient serine-threonine kinase belonging to AGC kinase family.
View Article and Find Full Text PDFExpert Opin Biol Ther
April 2016
b 2 University of California San Francisco, Mt. Zion Cancer Research Center, 2340 Sutter Street N461, San Francisco, CA, USA.
Introduction: Targeted therapy and immunotherapies are the novel pharmacologic treatment strategies for metastatic melanoma. BRAF and MEK inhibitors effectively block the hyperactivation of the MAPK pathway in BRAF mutant melanomas and also have several other effects on melanoma cells and on the immune response. The aim of this work is to discuss the rationale, evidence and perspectives of approaches combining target and immunotherapy against melanoma.
View Article and Find Full Text PDFClin Cancer Res
August 2015
Laboratory of Translational Cancer Medicine, Candiolo Cancer Institute-FPO IRCCS, Candiolo (Torino), Italy.
Monoclonal antibodies targeting the EGF receptor (EGFR) tyrosine kinase, such as cetuximab and panitumumab, achieve clinically meaningful responses in patients affected by head and neck and colorectal cancers. Despite this evidence of efficacy, no genomic abnormalities that robustly predict sensitivity to EGFR blockade have been yet identified. This suggests that, in some tumor contexts, EGFR dependency is not acquired during neoplastic transformation and rather reflects an aberrant declination of physiologic traits typical of normal tissue counterparts.
View Article and Find Full Text PDFSci Rep
May 2015
1] Department of Oncology, University of Torino, Torino, 10043, Italy [2] Candiolo Cancer Institute-FPO IRCCS, Candiolo, 10060, Italy [3] Center for Molecular Systems Biology, University of Torino, 10124, Torino, Italy.
Cellular protrusions are highly dynamic structures involved in fundamental processes, including cell migration and invasion. For a cell to migrate, its leading edge must form protrusions, and then adhere or retract. The spatial and temporal coordination of protrusions and retraction is yet to be fully understood.
View Article and Find Full Text PDFSci Transl Med
January 2015
Department of Oncology, University of Torino Medical School, 10060 Candiolo, Torino, Italy. Translational Cancer Medicine, Candiolo Cancer Institute-Fondazione del Piemonte per l'Oncologia (FPO) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 10060 Candiolo, Torino, Italy. National Institute of Biostructures and Biosystems, 00136 Rome, Italy.
Among patients with colorectal cancer who benefit from therapy targeted to the epidermal growth factor receptor (EGFR), stable disease (SD) occurs more frequently than massive regressions. Exploring the mechanisms of this incomplete sensitivity to devise more efficacious treatments will likely improve patients' outcomes. We tested therapies tailored around hypothesis-generating molecular features in patient-derived xenografts ("xenopatients"), which originated from 125 independent samples that did not harbor established resistance-conferring mutations.
View Article and Find Full Text PDFJ Cell Sci
March 2015
Candiolo Cancer Institute FPO-IRCCS, Candiolo, 10060 Turin, Italy Department of Oncology, University of Torino, 10126 Turin, Italy
Non-amoeboid cell migration is characterised by dynamic competition among multiple protrusions to establish new adhesion sites at the cell's leading edge. However, the mechanisms that regulate the decision to disassemble or to grow nascent adhesions are not fully understood. Here we show that, in endothelial cells, 3-phosphoinositide-dependent protein kinase 1 (PDK1) promotes focal adhesion (FA) turnover by controlling endocytosis of integrin αvβ3 in a PI3K-dependent manner.
View Article and Find Full Text PDFOncotarget
January 2015
Candiolo Cancer Institute - FPO IRCCS, Italy. Department of Oncology, University of Torino, Italy.
Constitutively active receptor tyrosine kinases (RTKs) are known oncogenic drivers and provide valuable therapeutic targets in many cancer types. However, clinical efficacy of RTK inhibitors is limited by intrinsic and acquired resistance. To identify genes conferring resistance to inhibition of the MET RTK, we conducted a forward genetics screen in the GTL-16 gastric cancer cell line, carrying MET amplification and exquisitely sensitive to MET inhibition.
View Article and Find Full Text PDFMol Oncol
February 2015
Candiolo Cancer Institute - FPO (IRCCS), Str. Prov. 142, 10060 Candiolo, Torino, Italy; Department of Oncology, University of Torino, Italy. Electronic address:
The inflammatory cytokine Tumor Necrosis Factor Alpha (TNF-α) is known to trigger invasive growth, a physiological property for tissue healing, turning into a hallmark of progression in cancer. However, the invasive response to TNF-α relies on poorly understood molecular mechanisms. We thus investigated whether it involves the MET oncogene, which regulates the invasive growth program by encoding the tyrosine kinase receptor for Hepatocyte Growth Factor (HGF).
View Article and Find Full Text PDFCancer Discov
September 2014
Catalan Institute of Oncology-Bellvitge Biomedical Research Institute, L'Hospitalet de Llobregat, Barcelona, Spain;
Unlabelled: Recently, there has been an increasing interest in the development and characterization of patient-derived tumor xenograft (PDX) models for cancer research. PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor and remain stable across passages. These models have been shown to be predictive of clinical outcomes and are being used for preclinical drug evaluation, biomarker identification, biologic studies, and personalized medicine strategies.
View Article and Find Full Text PDFOncotarget
August 2014
Department of Oncology, University of Torino, Candiolo, Torino, Italy; Candiolo Cancer Institute - FPO IRCCS, Candiolo, Torino, Italy.
CDT2/L2DTL/RAMP is one of the substrate receptors of the Cullin Ring Ubiquitin Ligase 4 that targets for ubiquitin mediated degradation a number of substrates, such as CDT1, p21 and CHK1, involved in the regulation of cell cycle and survival. Here we show that CDT2 depletion was alone able to induce the apoptotic death in 12/12 human cancer cell lines from different tissues, regardless of the mutation profile and CDT2 expression level. Cell death was associated to rereplication and to loss of CDT1 degradation.
View Article and Find Full Text PDFJ Cell Biol
August 2014
Department of Oncology and Center for Molecular Systems Biology, University of Turin, Turin 10060, ItalyDepartment of Oncology and Center for Molecular Systems Biology, University of Turin, Turin 10060, Italy Laboratory of Cell Migration, Candiolo Cancer Institute FPO-IRCCS, Candiolo 10060, Italy
Directional cell migration is of paramount importance in both physiological and pathological processes, such as development, wound healing, immune response, and cancer invasion. Here, we report that 3-phosphoinositide-dependent kinase 1 (PDK1) regulates epithelial directional migration and invasion by binding and activating myotonic dystrophy kinase-related CDC42-binding kinase α (MRCKα). We show that the effect of PDK1 on cell migration does not involve its kinase activity but instead relies on its ability to bind membrane phosphatidylinositol (3,4,5)-trisphosphate.
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