A5036401196- Lung Cancer Treatments and Mutations
- Chemical Reactions and Isotopes
- Glutathione Transferases and Polymorphisms
- Protein Tyrosine Phosphatases
- Melanoma and MAPK Pathways
- Microtubule and mitosis dynamics
- interferon and immune responses
- Cancer-related Molecular Pathways
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- PI3K/AKT/mTOR signaling in cancer
- Protein Degradation and Inhibitors
- Immunotherapy and Immune Responses
- Lung Cancer Research Studies
- Colorectal Cancer Treatments and Studies
- Immune Cell Function and Interaction
- Synthesis and biological activity
- Epigenetics and DNA Methylation
- Cellular transport and secretion
- Genomics and Chromatin Dynamics
- Cancer Cells and Metastasis
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Synthesis and Characterization of Heterocyclic Compounds
- Ocular Oncology and Treatments
Novartis (Switzerland)
2019-2024
Novartis Institutes for BioMedical Research
2019-2024
Memorial Sloan Kettering Cancer Center
2014-2023
Novartis (United States)
2020
Spanish National Cancer Research Centre
2008-2013
Kettering University
2013
Centro de Investigación del Cáncer
2011-2012
Small molecules spark NK cell response Immunotherapy is a powerful treatment for certain cancers. Yet those patients that do not respond, simultaneous strategies mobilize the immune system and directly target malignant cells may be more effective. Ruscetti et al. report combining two clinically approved cancer drugs promoted surveillance killing of KRAS-mutant lung tumors in mice (see Perspective by Cornen Vivier). The small molecules—a mitogen-activated protein kinase inhibitor...
Abstract The major histocompatibility complex I (MHC-1) presents antigenic peptides to tumor-specific CD8+ T cells. regulation of MHC-I by kinases is largely unstudied, even though many patients with cancer are receiving therapeutic kinase inhibitors. Regulators cell-surface HLA amounts were discovered using a pooled human kinome shRNA interference–based approach. Hits scoring highly subsequently validated additional RNAi and pharmacologic MAP2K1 (MEK), EGFR, RET as negative regulators...
Tetracycline or doxycycline (dox)-regulated control of genetic elements allows inducible, reversible and tissue specific regulation gene expression in mice. This approach provides a means to investigate protein function cell lineages at defined periods development disease. Efficient stable cDNAs non-coding (e.g. shRNAs) downstream the tetracycline-regulated element (TRE) requires robust tet-transactivator protein, commonly reverse tet-transactivator, rtTA. Most rtTA strains rely on promoters...
PP2A is a major tumor suppressor whose inactivation frequently found in wide spectrum of human tumors. In particular, deletion or epigenetic silencing genes encoding the B55 family regulatory subunits common feature breast cancer cells. A key player regulation PP2A/B55 phosphatase complexes cell cycle kinase MASTL (also known as Greatwall). During division, inhibition PP2A-B55 by required to maintain mitotic state, whereas and reactivation for exit. Despite its critical role progression...
FGFR1 was recently shown to be activated as part of a compensatory response prolonged treatment with the MEK inhibitor trametinib in several KRAS-mutant lung and pancreatic cancer cell lines. We hypothesize that other receptor tyrosine kinases (RTK) are also feedback-activated this context. Herein, we profile large panel lines for contribution RTKs feedback activation phospho-MEK following inhibition, using an SHP2 (SHP099) blocks RAS mediated by multiple RTKs. find RTK-driven widely exists...
Lung adenocarcinoma (LUAD), commonly driven by KRAS mutations, is responsible for 7% of all cancer mortality. The first allele-specific inhibitors were recently approved in LUAD, but the clinical benefit limited intrinsic and acquired resistance. LUAD predominantly arises from alveolar type 2 (AT2) cells, which function as facultative stem cells self-renewing replacing 1 (AT1) cells. Using genetically engineered mouse models, patient-derived xenografts, patient samples, we found inhibition...
Abstract Activating mutations in GNAQ/GNA11 occur over 90% of uveal melanomas (UMs), the most lethal melanoma subtype; however, targeting these oncogenes has proven challenging and inhibiting their downstream effectors show limited clinical efficacy. Here, we performed genome-scale CRISPR screens along with computational analyses cancer dependency gene expression datasets to identify inositol-metabolizing phosphatase INPP5A as a selective GNAQ/11-mutant UM cells vitro vivo. Mutant...
Cdc14 is an essential phosphatase in yeast but its role the mammalian cell cycle remains obscure. We report here that Cdc14b-knockout cells display unscheduled induction of multiple regulators resulting early entry into DNA replication and mitosis from quiescence. Cdc14b dephosphorylates Ser5 at C-terminal domain (CTD) RNA polymerase II, a major substrate cyclin-dependent kinases. Lack results increased CTD-Ser5 phosphorylation, epigenetic modifications mark active chromatin, transcriptional...
The Myb transcription factor is involved in the proliferation of hematopoietic cells, and deregulation its expression can lead to cancers such as leukemia. interacts with various proteins, including histone acetyltransferases p300 CBP. binds a small domain p300, KIX (p300KIX), inhibiting this interaction potential new drug discovery strategy oncology. available structures show that very shallow pocket domain, indicating it might be challenging identify inhibitors interaction. Here, we report...
Access to the cyclic depsipeptide FR900359 (FR), a selective Gq/11 protein inhibitor of high pharmacological interest and potential lead molecule for targeted therapy cancers with oncogenic GNAQ or GNA11 mutations (encoding Gq G11 respectively), has been challenging ever since its initial discovery more than three decades ago. The recent Chromobacterium vaccinii as cultivable FR producer enables development approaches leading high-yielding, scalable sustainable biotechnological process...