A5082672878- Lung Cancer Treatments and Mutations
- PI3K/AKT/mTOR signaling in cancer
- Advanced Breast Cancer Therapies
- Lung Cancer Research Studies
- HER2/EGFR in Cancer Research
- Cancer-related Molecular Pathways
- Cancer Immunotherapy and Biomarkers
- Neuroendocrine Tumor Research Advances
- Occupational and environmental lung diseases
- Cancer Research and Treatments
- Cancer Mechanisms and Therapy
- Immunotherapy and Immune Responses
- Colorectal Cancer Treatments and Studies
- Fibroblast Growth Factor Research
- HIV/AIDS drug development and treatment
- Electrochemical Analysis and Applications
- Lanthanide and Transition Metal Complexes
- Coffee research and impacts
- Crystal structures of chemical compounds
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Cancer Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Analytical Chemistry and Sensors
- X-ray Diffraction in Crystallography
University of Parma
2012-2025
Malignant pleural mesothelioma (MPM) is a progressive malignancy associated to the exposure of asbestos fibers. The most frequently inactivated tumor suppressor gene in MPM CDKN2A/ARF, encoding for cell cycle inhibitors p16INK4a and p14ARF, deleted about 70% cases. Considering high frequency alterations this gene, we tested cells efficacy palbociclib (PD-0332991), highly selective inhibitor cyclin-dependent kinase (CDK) 4/6. analyses were performed on panel lines two primary culture from...
Cell cycle regulators have gain attention as potential targets for anticancer therapy. Palbociclib is a selective inhibitor of the cyclin-dependent kinases 4 and 6 (CDK4/6), which coordinate G1-S transition. currently approved treatment hormone receptor positive, HER2-negative advanced breast cancer (BC) in association with letrozole or fulvestrant. In contrast, its efficacy triple negative BC (TNBC), either alone combined therapies, has not been fully investigated to date. Here we evaluated...
Abstract Triple Negative Breast Cancer (TNBC) is a challenging disease due to the lack of druggable targets; therefore, chemotherapy remains standard care and identification new targets high clinical priority. Alterations in components cell cycle machinery have been frequently reported cancer; given success obtained with CDK4/6 inhibitor palbocicib ER-positive BC, we explored potential combining this drug Rb-positive TNBC models. The simultaneous combination palbociclib paclitaxel exerted an...
Osimertinib is a third-generation EGFR-TKI with high selective potency against T790M-mutant NSCLC patients. Considering that osimertinib can lead to enhanced HER-2 expression on cell surface and overexpression mechanism of resistance osimertinib, this study was addressed investigate the potential combining trastuzumab emtansine (T-DM1) in order improve efficacy delay or overcome lines EGFR activating mutation T790M amplification.The effects combined T-DM1 proliferation, cycle, death,...
The third generation Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) osimertinib has been initially approved for T790M positive Non-Small Cell Lung Cancer (NSCLC) and more recently first-line treatment of EGFR-mutant negative NSCLC patients. Similarly to previous TKIs, despite the high response rate, disease progression eventually occurs current clinical research is focused on novel strategies delay emergence resistance. In this study we investigated combination with...
HER-2 represents a relatively new therapeutic target for non small cell lung cancer (NSCLC) patients. The incidence reported overexpression/amplification/mutations ranges from 2 to 20% in NSCLC. Moreover, amplification is potential mechanism of resistance tyrosine kinase inhibitors the epidermal growth factor receptor (EGFR-TKI) (about 10% cases). T-DM1, trastuzumab emtansine an antibody-drug conjugate composed by monoclonal antibody and microtubule polymerization inhibitor DM1. activity...
Background BCRP/ABCG2 emerged as an important multidrug resistance protein, because it confers to several classes of cancer chemotherapeutic agents and a number novel molecularly-targeted therapeutics such tyrosine kinase inhibitors. Gefitinib is orally active, selective EGFR inhibitor used in the treatment patients with advanced non small cell lung (NSCLC) carrying activating mutations. Membrane transporters may affect distribution accumulation gefitinib tumour cells; particular reduced...
Despite the initial response, all patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) eventually develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs). The EGFR-T790M secondary mutation is responsible for half of cases, while MET amplification has been associated in about 5-15% NSCLCs. Clinical findings indicate retained addiction resistant tumors on signaling. Therefore, we evaluated molecular mechanisms supporting therapeutic...
Fibroblast Growth Factor Receptors (FGFR1-4) have a critical role in the progression of several human cancers, including Squamous Non-Small-Cell Lung Cancer (SQCLC). Both non-selective and selective reversible FGFR inhibitors are under clinical investigation for treatment patients with tumors harboring alterations. Despite their potential efficacy, development these drugs has encountered challenges, toxicity, appearance drug resistance. Recent efforts been directed at irreversible...
Abemaciclib is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6 that inhibits the transition from G1 to S phase cell cycle by blocking downstream CDK4/6-mediated phosphorylation Rb. The effects abemaciclib alone or combined with third-generation epidermal growth factor receptor (EGFR) tyrosine kinase (TKI) osimertinib were examined in a panel PC9 HCC827 osimertinib-resistant non-small lung cancer (NSCLC) lines carrying EGFR-dependent -independent mechanisms intrinsic acquired...
Immunotherapy has significantly changed the treatment landscape for advanced non-small-cell lung cancer (NSCLC) with introduction of drugs targeting programmed cell death protein-1 (PD-1) and ligand-1 (PD-L1). In particular, addition anti-PD-1 antibody pembrolizumab to platinum-pemetrexed chemotherapy resulted in a improved overall survival patients non-squamous NSCLC, regardless PD-L1 expression. this preclinical study, we investigated whether can modulate expression NSCLC lines, thus...
Abstract Background The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two strategies have been explored to inhibit this pivotal molecule epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by antibodies such as cetuximab trastuzumab or tyrosine-kinase inhibitors gefitinib erlotinib has proven effective the of advanced NSCLC. Results In study we potential combining either with...
A prominent role in the pathogenesis of squamous cell carcinoma lung (SQCLC) has been attributed to aberrant activation PI3K signaling pathway, due amplification or mutations p110α subunit class I phosphatidylinositol 3-kinase (PIK3CA) gene. The aim our study was determine whether different genetic alterations PIK3CA affect biologic properties SQCLC and evaluate response specific targeting agents vitro vivo. effects NVP-BEZ235, NVP-BKM120, NVP-BYL719 on two-dimensional/three-dimensional...
// Claudia Fumarola 1 , Daniele Cretella Silvia La Monica Mara A. Bonelli Roberta Alfieri Cristina Caffarra Federico Quaini Denise Madeddu Angela Falco Andrea Cavazzoni Graziana Digiacomo Giulia Mazzaschi Valentina Vivo 2 Elisabetta Barocelli Marcello Tiseo 3 Pier Giorgio Petronini 1, * and Ardizzoni 4, Department of Medicine Surgery, University Parma, Italy Food Drug Department, Medical Oncology Unit, Hospital 4 Division Oncology, Sant'Orsola-Malpighi Hospital, Bologna, Joint last authors...
Background: Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated to asbestos exposure. One of the most frequent genetic alteration in MPM patients CDKN2A/ARF loss, leading aberrant activation Rb pathway. In cells, we previously demonstrated therapeutic efficacy targeting this signaling with CDK4/6 inhibitor palbociclib combination PI3K/mTOR inhibitors. Here, investigated whether such may have impact on cell energy metabolism. Methods: The study was performed cells...
Advanced hepatocarcinoma (HCC) is an aggressive malignancy with poor prognosis and limited treatment options. Alterations of the cyclin D-CDK4/6-Rb pathway occur frequently in HCC, providing rationale for its targeting at least a molecular subset HCC. In panel HCC cell lines, we investigated whether CDK4/6 inhibitor palbociclib might improve efficacy regorafenib, powerful multi-kinase approved as second-line advanced after sorafenib failure currently under clinical investigation first-line...