Publications by authors named "E Baldelli"
Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS- and autophagy-dependent growth. Inhibition of the KRAS-RAF-MEK-ERK pathway enhances autophagic flux and dependency, and concurrent treatment with the nonspecific autophagy inhibitor chloroquine (CQ) and ERK-MAPK pathway inhibitors can synergistically block PDAC growth. However, CQ is limited in terms of specificity and potency.
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- Changes in cholesterol-related factors are important in Alzheimer's disease (AD), but their timing, specific links, and relationship to genetic factors are still unclear.
- The study measured Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) and specific cholesterol metabolites in the cerebrospinal fluid (CSF) and serum of patients with different cognitive decline stages, focusing on AD and mild cognitive impairment (MCI-AD) with respect to genetic carriers.
- Results showed that PCSK9 and certain cholesterol markers in AD patients, especially genetic carriers, could act as specific indicators of lipid changes associated with AD progression, which weren’t observed in MCI-AD patients.
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- Mutations in the PIK3CA/AKT/mTOR signaling pathway are prevalent in metastatic breast cancers (MBCs), leading researchers to investigate how these genetic changes relate to the activation of proteins in this pathway.
- In a study involving 171 MBC patients, genetic alterations were analyzed through next-generation sequencing, while protein activation levels were measured using advanced proteomic methods to see how they correlated with treatment responses.
- Results showed that nearly half of the cases had oncogenic alterations, but genetic profiles were not strong predictors of protein activity, highlighting the importance of measuring phosphoprotein levels alongside genomic data for better understanding and treatment of MBCs.
Background: Tumor heterogeneity is a main contributor of resistance to anti-cancer targeted agents though it has proven difficult to study. Unfortunately, model systems to functionally characterize and mechanistically study dynamic responses to treatment across coexisting subpopulations of cancer cells remain a missing need in oncology.
Methods: Using single cell cloning and expansion techniques, we established monoclonal cell subpopulations (MCPs) from a commercially available epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer cell line.
To delineate the mechanisms by which the ERK1 and ERK2 mitogen-activated protein kinases support mutant KRAS-driven cancer growth, we determined the ERK-dependent phosphoproteome in KRAS-mutant pancreatic cancer. We determined that ERK1 and ERK2 share near-identical signaling and transforming outputs and that the KRAS-regulated phosphoproteome is driven nearly completely by ERK. We identified 4666 ERK-dependent phosphosites on 2123 proteins, of which 79 and 66%, respectively, were not previously associated with ERK, substantially expanding the depth and breadth of ERK-dependent phosphorylation events and revealing a considerably more complex function for ERK in cancer.
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