A5034617053- Cancer, Hypoxia, and Metabolism
- Colorectal Cancer Treatments and Studies
- Lung Cancer Treatments and Mutations
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- interferon and immune responses
- Cancer-related Molecular Pathways
- Sarcoma Diagnosis and Treatment
- Microtubule and mitosis dynamics
- Gene expression and cancer classification
- Molecular Biology Techniques and Applications
- Bone Tumor Diagnosis and Treatments
- Protein Degradation and Inhibitors
- Bioinformatics and Genomic Networks
- Quinazolinone synthesis and applications
- Cancer therapeutics and mechanisms
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Computational Drug Discovery Methods
- PI3K/AKT/mTOR signaling in cancer
- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- Melanoma and MAPK Pathways
- Advanced Breast Cancer Therapies
Nerviano Medical Sciences
2013-2022
University of Milan
2015
Candiolo Cancer Institute
2015
University of Turin
2015
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
2015
Ignyta (United States)
2015
IFOM
2015
Institut Pasteur
2000
A bottleneck in drug discovery is the identification of molecular targets a compound (mode action, MoA) and its off-target effects. Previous approaches to elucidate MoA include analysis chemical structures, transcriptional responses following treatment, text mining. Methods based on require least amount information can be quickly applied new compounds. Available methods are inefficient not able support network pharmacology. We developed an automatic robust approach that exploits similarity...
Abstract Activated ALK and ROS1 tyrosine kinases, resulting from chromosomal rearrangements, occur in a subset of non–small cell lung cancers (NSCLC) as well other tumor types their oncogenic relevance actionable targets has been demonstrated by the efficacy selective kinase inhibitors such crizotinib, ceritinib, alectinib. More recently, low-frequency rearrangements TRK kinases have described NSCLC, colorectal carcinoma, glioblastoma, Spitzoid melanoma. Entrectinib, whose discovery...
In metastatic colorectal cancer (CRC), actionable genetic lesions represent potential clinical opportunities. NTRK1, 2, and 3 gene rearrangements encode oncogenic fusions of the tropomyosin-receptor kinase (TRK) family receptor tyrosine kinases in different tumor types. The TPM3-NTRK1 rearrangement is a recurring event CRC that renders tumors sensitive to TRKA inhibitors preclinical models. We identified abnormal expression protein liver metastases patient refractory standard therapy....
Abstract Cancer cells within a tumour have heterogeneous phenotypes and exhibit dynamic plasticity. How to evaluate such heterogeneity its impact on outcome drug response is still unclear. Here, we transcriptionally profile 35,276 individual from 32 breast cancer cell lines yield single atlas. We find high degree of in the expression biomarkers. then train deconvolution algorithm atlas determine line composition bulk gene profiles biopsies, thus enabling line-based patient stratification....
The NTRK1 gene encodes Tropomyosin-related kinase A (TRKA), the high-affinity Nerve Growth Factor Receptor. was originally isolated from a colorectal carcinoma (CRC) sample as component of somatic rearrangement (TPM3-NTRK1) resulting in expression oncogenic chimeric protein TPM3-TRKA, but there has been no subsequent report regarding relevance this oncogene CRC. KM12 human CRC cell line expresses TPM3-TRKA and is hypersensitive to TRKA inhibition. We detailed characterization TPM3-NTRK1...
Chordomas are rare bone tumors with no approved therapy. These express several activated tyrosine kinase receptors, which prompted attempts to treat patients inhibitors. Although clinical benefit was observed in phase II trials imatinib and sorafenib, sporadically also EGFR inhibitors, therapies evaluated date have shown modest activity. With the goal of identifying new drugs immediate therapeutic potential for chordoma patients, we collected clinically other advanced inhibitors MET, PDGFRβ,...
Activated anaplastic lymphoma kinase (ALK) gene fusions are recurrent events in a small fraction of colorectal cancers (CRCs), although these have not yet been exploited as other malignancies. We detected ALK protein expression by immunohistochemistry and rearrangements fluorescence situ hybridisation the ALKA-372-001 phase I study pan-Trk, ROS1, inhibitor entrectinib. One out 487 CRCs showed positivity with peculiar pattern that prompted further characterisation targeted sequencing using...
Cdc7 kinase is an essential protein that promotes DNA replication in eukaryotic organisms. Genetic evidence indicates inhibition can cause selective tumor-cell death a p53-independent manner, supporting the rationale for developing small-molecule inhibitors treatment of cancers. In this paper, synthesis and structure-activity relationships 2-heteroaryl-pyrrolopyridinones, first potent inhibitors, are described. Starting from 2-pyridin-4-yl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one,...
Microarrays have been widely used for the analysis of gene expression and several commercial platforms are available. The combined use multiple can overcome inherent biases each approach, may represent an alternative that is complementary to RT-PCR identification more robust changes in profiles. In this paper, we statistical functional cross platform validation two oligonucleotide-based technologies, Affymetrix (AFFX) Applied Biosystems (ABI), differentially expressed genes. study, analysed...
// Diego Carrella 1 , Isabella Manni 3 Barbara Tumaini Rosanna Dattilo 2 Federica Papaccio Margherita Mutarelli Francesco Sirci Carla A. Amoreo 4 Marcella Mottolese Manuela Iezzi 5 Laura Ciolli Valentina Aria 6 Roberta Bosotti 7 Antonella Isacchi Fabrizio Loreni Alberto Bardelli 8,9 Vittorio E. Avvedimento 10 di Bernardo 1,11 and Luca Cardone Telethon Institute of Genetics Medicine, Pozzuoli, Naples, Italy Department Hematology, Oncology Molecular Biobank Unit, Istituto Superiore...
The success of Imatinib (IM) therapy in chronic myeloid leukemia (CML) is compromised by the development IM resistance and a limited effect on hematopoietic stem cells. Danusertib (formerly PHA-739358) potent pan-aurora ABL kinase inhibitor with activity against known BCR-ABL mutations, including T315I. Here, individual contribution both signaling pathways to therapeutic as well mechanisms underlying and, consequence, strategies overcome were investigated. Starting at low concentrations,...
In colorectal cancer patients, chromosomal rearrangements involving NTRK1 gene (encoding the TRKA protein) are shown in a small subset of patients and associated with constitutive activation kinase domain TRKA. turn, activated TRKA-fusion proteins proliferation survival tumors. Here we report identification functional characterization new SCYL3-NTRK1 fusion 61-year-old patient. To our knowledge, this protein has never been previously documented oncological patients. We show that novel is...
Poly(ADP-ribose) polymerase-2 (PARP2) belongs to the ADP-ribosyltransferase family of enzymes that catalyze addition ADP-ribose units acceptor proteins, thus affecting many diverse cellular processes. In particular, PARP2 shares with PARP1 and, as recently highlighted, PARP3 sole property being catalytically activated by DNA-strand breaks, implying key downstream functions in response DNA damage for both enzymes. However, evidence from several studies suggests unique additional processes,...
Next-Generation Sequencing (NGS) is a high-throughput technology widely applied to genome sequencing and transcriptome profiling. RNA-Seq uses NGS reveal RNA identities quantities in given sample. However, it produces huge amount of raw data that need be preprocessed with fast effective computational methods. can look at different populations RNAs, including ncRNAs. Indeed, the last few years, several ncRNAs pipelines have been developed for analysis from experiments. In this paper, we...
Abstract Background RNA-Seq is a well-established technology extensively used for transcriptome profiling, allowing the analysis of coding and non-coding RNA molecules. However, this produces vast amount data requiring sophisticated computational approaches their than other traditional technologies such as Real-Time PCR or microarrays, strongly discouraging non-expert users. For reason, dozens pipelines have been deployed data. Although interesting, these present several limitations usage...
The protein tyrosine kinase ZAP-70 is implicated in the early steps of T-cell antigen receptor (TCR) signaling. Binding to phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) TCR ζ chain through its two src-homology 2 (SH2) domains results coupled phosphorylation on multiple residues, mediated by Src kinases including Lck as well autophosphorylation. mechanism following binding still not completely understood. Here we investigated effect intramolecular interactions and...
A transcriptional signature of the pan-cyclin-dependent kinase (Cdk) inhibitor PHA-793887 was evaluated as a potential pharmacodynamic and/or response biomarker in tumor and skin biopsies from patients treated phase I clinical study. We first analyzed expression number known E2F-dependent genes that were predicted to be modulated after Cdk2 Cdk4 inhibition xenograft samples mice with compound. This panel 58 selected then seven dose escalation trial solid tumors. Quantitative real-time PCR or...
Chordomas are rare, slowly growing tumors with high medical need, arising in the axial skeleton from notochord remnants. The transcription factor "brachyury" represents a distinctive molecular marker and key oncogenic driver of chordomas. Tyrosine kinase receptors also expressed, but so far inhibitors have not shown clear clinical efficacy chordoma patients. need for effective therapies is extremely high, paucity established cell lines has limited preclinical research. Here we describe...
The generation of biological data on wide panels tumor cell lines is recognized as a valid contribution to the cancer research community. However, laboratories can benefit from this knowledge only after identity each individual line used in experiments verified and matched external sources. Among methods employed assess identity, DNA fingerprinting by profiling Short Tandem Repeat (STR) at variable loci has become method choice. analysis sometimes complicated their intrinsic genetic...
Abstract The tyrosine threonine kinase TTK, also known as Monopolar Spindle 1 (MPS1), is a conserved found to be highly expressed in number of human tumors different origin. TTK activity plays critical role the control mitosis, regulating spindle assembly checkpoint (SAC), mitotic mechanism required for proper chromosome alignment and segregation during cellular division. this has been shown proficient up-regulated aneuploid tumors, common feature measured approximately 90% solid 70%...