A5061100797- DNA Repair Mechanisms
- Lung Cancer Treatments and Mutations
- Genetic factors in colorectal cancer
- PI3K/AKT/mTOR signaling in cancer
- RNA modifications and cancer
- Nutrition, Genetics, and Disease
- Cancer-related Molecular Pathways
- Cancer therapeutics and mechanisms
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- Melanoma and MAPK Pathways
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Metabolomics and Mass Spectrometry Studies
- MicroRNA in disease regulation
- PARP inhibition in cancer therapy
- RNA and protein synthesis mechanisms
- Metal complexes synthesis and properties
- Cancer-related molecular mechanisms research
- Ovarian cancer diagnosis and treatment
- FOXO transcription factor regulation
- Genomics and Rare Diseases
- Ubiquitin and proteasome pathways
- Cancer, Lipids, and Metabolism
- Chronic Lymphocytic Leukemia Research
Mario Negri Institute for Pharmacological Research
2014-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2022
Cleveland Clinic
2000
// Laura Brunelli 1,* , Elisa Caiola 2,* Mirko Marabese 2 Massimo Broggini and Roberta Pastorelli 1 Protein Gene Biomarkers Unit, Department of Environmental Health Sciences, IRCCS-Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy Laboratory Molecular Pharmacology, Oncology, * The authors contributed equally to this work Correspondence: Pastorelli, email: Broggini, Keywords : KRAS, mutations, NSCLC, metabolomics, mass-spectrometry Received February 18, 2014 Accepted...
// Mirko Marabese 1,* , Monica Ganzinelli 2,* Marina C. Garassino 2 Frances A. Shepherd 3 Sheila Piva 4 Elisa Caiola 1 Marianna Macerelli Anna Bettini 5 Calogero Lauricella 6 Irene Floriani Gabriella Farina Flavia Longo 7 Lucia Bonomi M. Agnese Fabbri 8 Silvio Veronese Silvia Marsoni 9 Massimo Broggini and Eliana Rulli Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy Fondazione Nazionale dei Tumori, Princess Margaret Cancer Center, University of...
// Elisa Caiola 1 , Daniela Salles 2 Roberta Frapolli 3 Monica Lupi Giuseppe Rotella 4 Anna Ronchi 5 Marina Chiara Garassino 6 Nikola Mattschas Stefano Colavecchio Massimo Broggini Lisa Wiesmüller Mirko Marabese Laboratory of Molecular Pharmacology, Department Oncology, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy Obstetrics and Gynecology the University Ulm, Germany Cancer Environmental Health Sciences, Centro Nazionale Informazione Tossicologiche, Fondazione...
Non–small-cell lung cancer (NSCLC) is a heterogeneous disease, with multiple different oncogenic mutations. Approximately 25–30% of NSCLC patients present KRAS mutations, which confer poor prognosis and high risk tumor recurrence. About half NSCLCs activating lesions also have deletions or inactivating mutations in the serine/threonine kinase 11 (LKB1) gene. Loss LKB1 on KRAS-mutant background may represent significant source heterogeneity contributing to response therapy. Here, we employed...
Abstract Oncogenes induce metabolic reprogramming on cancer cells. Recently, G12C KRAS mutation in isogenic NSCLC cell line has been shown to be a key player promoting rewiring mainly through the regulation of glutamine metabolism fuel growth and proliferation. Even though lines possessing many genetic backgrounds primary they derive from could valuable pre-clinical model, do not have additional complexity present whole tumor that impact metabolism. This preliminary study is aimed explore...
Non-small-cell lung cancer (NSCLC) cell lines vary in their sensitivity to glutaminase inhibitors, so it is important identify the metabolic assets underling efficacy cells. Even though specific genetic lesions such as KRAS and LKB1 have been associated with reliance on glutamine for needs, we found no distinction between inhibitor CB-839 resistant phenotypes NSCLC cells or without these alterations. We demonstrated close relationship environmental alanine uptake catabolism. This response...
Drug resistance is one of the major obstacles limiting activity anticancer agents. Activation DNA repair mechanism often accounts for increase to cancer chemotherapy.We present evidence that nemorubicin, a doxorubicin derivative currently in clinical evaluation, acts through action different from classical anthracyclines, requiring an intact nucleotide excision (NER) system exert its activity. Cells made resistant nemorubicin show increased sensitivity UV damage. We have analysed and...
Abstract Non-Small-Cell Lung Cancer (NSCLC) is a poorly chemosensitive tumor and targeted therapies are only used for about 15% of patients where specific driving druggable lesion observed (EGFR, ALK, ROS). KRAS one the most frequently mutated genes in NSCLC harboring these mutations do not benefit from treatments. Sorafenib, multi-target tyrosine kinase inhibitor, was proposed as potentially active drug KRAS-mutated patients, but clinical trials results were conclusive. Here we show that...
// Elisa Caiola 1, * , Laura Brunelli 2, Mirko Marabese 1 Massimo Broggini Monica Lupi 3 Roberta Pastorelli 2 Laboratory of Molecular Pharmacology, Department Oncology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy Protein and Gene Biomarkers Unit, Mass Spectrometry, Environmental Health Sciences, Cancer These authors have contributed equally to this work Correspondence to: Broggini, email: massimo.broggini@marionegri.it Pastorelli, roberta.pastorelli@marionegri.it...
IntroductionPreclinical models recently unveiled the vulnerability of LKB1/KRAS comutated NSCLC to metabolic stress-based treatments. Because miR-17 is a potential epigenetic regulator LKB1, we hypothesized that wild-type LKB1 (LKB1WT) with high expression may be sensitive an energetic stress condition, and eligible for frailties-based therapeutic intervention.MethodsWe took advantage cell lines different combinations KRAS mutation deletion patient-derived xenografts (PDXs) (LKB1WT/miR-17...
MicroRNAs were described to target mRNA and regulate the transcription of genes involved in processes de-regulated tumorigenesis, such as proliferation, differentiation survival. In particular, miRNA let-7 has been suggested expression KRAS gene, a common mutated gene non-small cell lung cancer (NSCLC), through complementary site (LCS) 3'UTR mRNA. We have reported analysis performed on role polymorphism located KRAS-LCS (rs61764370) which is disruption NSCLC patients enrolled within TAILOR...
The Phosphatidyl inositol-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and c-Met signaling pathways are often deregulated in cancer. two interconnected at least has been implicated drug resistance. aim the study was to assess ovarian cancer preclinical models, efficacy tolerability a dual PI3K mTOR inhibitor (PF-05212384 or gedatolisib) (crizotinib) either as single agents combination. In vitro, both PF-05212384 crizotinib showed concentration dependent activity cell lines....
Platinum resistance is an unmet medical need in ovarian carcinoma. Molecular biomarkers to predict the response platinum-based therapy could allow patient stratification and alternative therapeutic strategies early clinical management. Sensitivity platinum are partially determined by tumor’s intrinsic DNA repair activities, including nucleotide excision (NER) base (BER). We investigated role of NER proteins—ERCC1, XPF, ERCC1/XPF complex—and BER protein polymerase β, as possible cisplatin...
Two recently discovered genetic abnormalities substantially increase the risk of venous thromboembolism. Yet we do not advocate screening for these except in cases which information gained would affect course action.
The RAS/RAF/MEK/ERK pathway is one of the most downregulated in cancer. Inhibitors RAF and MEK have established clinical use while ERK inhibitors recently faced clinic. We aimed to generate resistant cell lines which could be helpful for defining new combinations able overcome resistance.the human NSCLC line NCI-H727, sensitive both inhibitors, was treated with increasing concentrations MEK162 (as inhibitor) or SCH772984 as inhibitor.we successfully obtained a subline (H727/MEK, after 40...
Liver kinase B1 (LKB1/STK11) is the second tumor suppressor gene most frequently mutated in non-small-cell lung cancer (NSCLC) and its activity impaired about half KRAS-mutated NSCLCs. Nowadays, no effective therapies are available for patients having these mutations. To highlight new vulnerabilities of this subgroup tumors exploitable to design specific we screened an US FDA-approved drug library using isogenic system wild-type (WT) or deleted LKB1. Among eight hit compounds, Birinapant,...