A5063355877- Cancer-related Molecular Pathways
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
- Virus-based gene therapy research
- RNA Research and Splicing
- Cancer Research and Treatments
- Molecular Biology Techniques and Applications
- DNA Repair Mechanisms
- Chemical Synthesis and Analysis
- Cancer, Hypoxia, and Metabolism
- Click Chemistry and Applications
- Microtubule and mitosis dynamics
- Carcinogens and Genotoxicity Assessment
- HER2/EGFR in Cancer Research
- Radiopharmaceutical Chemistry and Applications
- Marine Sponges and Natural Products
- Monoclonal and Polyclonal Antibodies Research
- Synthesis and Biological Activity
- Peptidase Inhibition and Analysis
- Microbial Natural Products and Biosynthesis
- Epigenetics and DNA Methylation
- Cell death mechanisms and regulation
- Lung Cancer Research Studies
- Cancer-related gene regulation
- Lung Cancer Treatments and Mutations
Spanish National Cancer Research Centre
2005-2022
PharmaMar (Spain)
2012-2022
Weizmann Institute of Science
1999-2015
Centro de Investigación del Cáncer
2008
Centro Nacional de Epidemiología
2007
Light Prescriptions Innovators (Spain)
2006
Tel Aviv University
2001
Icahn School of Medicine at Mount Sinai
2001
St. Jude Children's Research Hospital
2001
University of Washington Medical Center
2000
The p53 tumor suppressor protein, a key regulator of cellular responses to genotoxic stress, is stabilized and activated after DNA damage. rapid activation by ionizing radiation radiomimetic agents largely dependent on the ATM kinase. phosphorylated shortly damage, resulting in enhanced stability activity p53. Mdm2 oncoprotein pivotal negative In response drugs, undergoes ATM-dependent phosphorylation prior accumulation. This results decrease its reactivity with 2A10 monoclonal antibody....
We have defined the mechanism of action lurbinectedin, a marine-derived drug exhibiting potent antitumor activity across several cancer cell lines and tumor xenografts. This drug, currently undergoing clinical evaluation in ovarian, breast, small lung patients, inhibits transcription process through (i) its binding to CG-rich sequences, mainly located around promoters protein-coding genes; (ii) irreversible stalling elongating RNA polymerase II (Pol II) on DNA template specific degradation...
Werner's syndrome is a human autosomal recessive disorder leading to premature aging. The mutations responsible for this have recently been localized gene (<i>WRN</i>) encoding protein that possesses DNA helicase and exonuclease activities. Patients carrying <i>WRN</i> exhibit an elevated rate of cancer, accompanied by increased genomic instability. latter features are also characteristic the loss function p53, tumor suppressor very frequently inactivated in cancer. Moreover, changes...
Vorinostat (suberoylanilide hydroxamic acid, SAHA), an inhibitor of class I and II histone deacetylases, has been approved for the treatment cutaneous T-cell lymphoma. In spite emerging information on effect vorinostat in many types cancer, little is yet known about this drug's mechanism action, which essential its proper use combination therapy. We investigated alterations gene expression profile over time lymphoma cells treated with vorinostat. Subsequently, we evaluated inhibitors PI3K,...
Abstract eEF1A2 is one of the isoforms alpha subunit eukaryotic Elongation Factor 1. It overexpressed in human tumors and endowed with oncogenic properties, favoring tumor cell proliferation while inhibiting apoptosis. We demonstrate that plitidepsin, an antitumor agent marine origin has successfully completed a phase-III clinical trial for multiple myeloma, exerts its activity by targeting eEF1A2. The drug interacts K D 80 nM target residence time circa 9 min. This protein was also...
Systemic treatment with the active transcription inhibitor lurbinectedin aims at inducing tumor cell death in hyperproliferative neoplasms. Here we show that induced by reinstates and enhances systemic anticancer immune responses. Lurbinectedin showed traits of immunogenic death, including exposure calreticulin, release ATP, exodus high mobility group box 1 (HMGB1) type interferon responses vitro. treated cells antitumor immunity when injected into immunocompetent animals transplanted...
A bstract : The p53 tumor suppressor protein provides a major anti‐cancer defense mechanism, as underscored by the fact that gene is most frequent target for genetic alterations in human cancer. Recent work has led to realization lies at hub of very complex network signaling pathways integrate variety intracellular and extracellular inputs. Part this consists an array autoregulatory feedback loops, where exhibits intricate interactions with other proteins known play important roles...
In eukaryotic cells, cyclin-dependent kinase (CDK) complexes regulate the temporal progression of cells through cell cycle. Deregulation in cycle is an essential component evolution cancer. Here, we validate CDK1 and CDK2 as potential therapeutic targets using novel selective small-molecule inhibitors cyclin B1/CDK1 E2/CDK2 enzyme (CDKi). Flow cytometry-based methods were developed to assess intracellular retinoblastoma (Rb) phosphorylation show inhibition CDK pathway. Tumor treated with...
With the idea to discover novel genes involved in proliferation, we have performed a genome-wide loss-of-function genetic screen identify additional putative tumor suppressor genes. We previously identified five belonging different biochemical families. In this report, focused on study of one these designated S-adenosylhomocysteine hydrolase (SAHH), which has also been an independent short hairpin RNA screening. SAHH inactivation confers resistance both p53 and p16(INK4)-induced...
Ectopic expression of conditional murine p53 (p53val135) and oncogenic ras is enough to induce a senescent-like growth arrest at the restrictive temperature. We took advantage this cellular system identify new key players in /p53-induced senescence. Applying retroviral-based genetic screen, we obtained an antisense RNA fragment against PPP1CA, catalytic subunit protein phosphatase 1α, whose loss function bypasses Expression specific short hairpin (sh)RNA PPP1CA impairs p53-dependent...
Tumorigenesis occurs when the mechanisms involved in control of tissue homeostasis are disrupted and cells stop responding to physiological signals. Therefore, genes capable desensitizing tumoral from signals may provide a selective advantage within mass influence outcome disease. We undertook large-scale genetic screen identify able alter cellular response once tumorigenesis has begun. identified MAP17, small 17 kDa non-glycosylated membrane protein previously by differential display being...
We undertook a large-scale genetic screen to identify genes able alter the cellular response physiological signals and provide selective advantage once tumorigenesis has begun. identified MAP17, small 17 kDa non-glycosylated membrane protein previously identified, being overexpressed in carcinomas. found that MAP17 is great variety of human Immunohistochemical analysis during cancer progression shows, at least prostate ovarian carcinomas, overexpression strongly correlates with tumoral (P <...
Through several not-fully-characterised moonlighting functions, translation elongation factor eEF1A2 is known to provide a fitness boost cancer cells. Furthermore, has been demonstrated confer neoplastic characteristics on preneoplastic, nontumourigenic precursor We have previously shown that the target of plitidepsin, marine drug currently in development for treatment. Herein, we characterised new signalling pathway through which promotes tumour cell survival. Previously unknown binding...