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  1. Article ; Online: Advancing precision rheumatology through tissue and blood profiling.

    Kalliolias, George D / Papavassiliou, Athanasios G

    Nature reviews. Rheumatology

    2024  

    Language English
    Publishing date 2024-04-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2491532-4
    ISSN 1759-4804 ; 1759-4790
    ISSN (online) 1759-4804
    ISSN 1759-4790
    DOI 10.1038/s41584-024-01115-7
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    Zs.A 6338: Show issues Location:
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  2. Article ; Online: Tackling the "Bottleneck" of Non-Small Cell Lung Cancer Pathobiology.

    Papavassiliou, Kostas A / Papavassiliou, Athanasios G

    Archives of medical research

    2023  Volume 54, Issue 4, Page(s) 350–351

    MeSH term(s) Humans ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms
    Language English
    Publishing date 2023-04-05
    Publishing country United States
    Document type Letter
    ZDB-ID 1156844-6
    ISSN 1873-5487 ; 0188-4409 ; 0188-0128
    ISSN (online) 1873-5487
    ISSN 0188-4409 ; 0188-0128
    DOI 10.1016/j.arcmed.2023.03.007
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  3. Article ; Online: Inhibition of the RAF/MEK/ERK Signaling Cascade in Pancreatic Cancer: Recent Advances and Future Perspectives.

    Adamopoulos, Christos / Cave, Donatella Delle / Papavassiliou, Athanasios G

    International journal of molecular sciences

    2024  Volume 25, Issue 3

    Abstract: Pancreatic cancer represents a formidable challenge in oncology, primarily due to its aggressive nature and limited therapeutic options. The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC), the main form of pancreatic cancer, remains ... ...

    Abstract Pancreatic cancer represents a formidable challenge in oncology, primarily due to its aggressive nature and limited therapeutic options. The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC), the main form of pancreatic cancer, remains disappointingly poor with a 5-year overall survival of only 5%. Almost 95% of PDAC patients harbor Kirsten rat sarcoma virus (KRAS) oncogenic mutations. KRAS activates downstream intracellular pathways, most notably the rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling axis. Dysregulation of the RAF/MEK/ERK pathway is a crucial feature of pancreatic cancer and therefore its main components, RAF, MEK and ERK kinases, have been targeted pharmacologically, largely by small-molecule inhibitors. The recent advances in the development of inhibitors not only directly targeting the RAF/MEK/ERK pathway but also indirectly through inhibition of its regulators, such as Src homology-containing protein tyrosine phosphatase 2 (SHP2) and Son of sevenless homolog 1 (SOS1), provide new therapeutic opportunities. Moreover, the discovery of allele-specific small-molecule inhibitors against mutant KRAS variants has brought excitement for successful innovations in the battle against pancreatic cancer. Herein, we review the recent advances in targeted therapy and combinatorial strategies with focus on the current preclinical and clinical approaches, providing critical insight, underscoring the potential of these efforts and supporting their promise to improve the lives of patients with PDAC.
    MeSH term(s) Humans ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Fibrosarcoma ; MAP Kinase Signaling System/genetics ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism ; Proto-Oncogene Proteins c-raf/antagonists & inhibitors ; Proto-Oncogene Proteins c-raf/metabolism
    Chemical Substances Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2) ; Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2) ; Proto-Oncogene Proteins c-raf (EC 2.7.11.1)
    Language English
    Publishing date 2024-01-28
    Publishing country Switzerland
    Document type Review ; Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25031631
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  4. Article: Targeting TLR Signaling Cascades in Systemic Lupus Erythematosus and Rheumatoid Arthritis: An Update.

    Kalliolias, George D / Basdra, Efthimia K / Papavassiliou, Athanasios G

    Biomedicines

    2024  Volume 12, Issue 1

    Abstract: Evidence from animal models and human genetics implicates Toll-like Receptors (TLRs) in the pathogenesis of Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). Endosomal TLRs sensing nucleic acids were proposed to induce lupus-promoting ... ...

    Abstract Evidence from animal models and human genetics implicates Toll-like Receptors (TLRs) in the pathogenesis of Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). Endosomal TLRs sensing nucleic acids were proposed to induce lupus-promoting signaling in dendritic cells, B cells, monocytes, and macrophages. Ligation of TLR4 in synovial macrophages and fibroblast-like synoviocytes (FLSs) by endogenous ligands was suggested to induce local production of mediators that amplify RA synovitis. Inhibition of TLRs using antagonists or monoclonal antibodies (mAbs) that selectively prevent extracellular or endosomal TLR ligation has emerged as an attractive treatment strategy for SLE and RA. Despite the consistent success of selective inhibition of TLR ligation in animal models, DV-1179 (dual TLR7/9 antagonist) failed to achieve pharmacodynamic effectiveness in SLE, and NI-0101 (mAb against TLR4) failed to improve arthritis in RA. Synergistic cooperation between TLRs and functional redundancy in human diseases may require pharmacologic targeting of intracellular molecules that integrate signaling downstream of multiple TLRs. Small molecules inhibiting shared kinases involved in TLR signaling and peptidomimetics disrupting the assembly of common signalosomes ("Myddosome") are under development. Targeted degraders (proteolysis-targeting chimeras (PROTACs)) of intracellular molecules involved in TLR signaling are a new class of TLR inhibitors with promising preliminary data awaiting further clinical validation.
    Language English
    Publishing date 2024-01-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines12010138
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  5. Article ; Online: mTOR Signaling: Recent Progress.

    Gargalionis, Antonios N / Papavassiliou, Kostas A / Papavassiliou, Athanasios G

    International journal of molecular sciences

    2024  Volume 25, Issue 5

    Abstract: In the intricate landscape of human biology, the mechanistic target of rapamycin (mTOR) emerges as a key regulator, orchestrating a vast array of processes in health and disease [ ... ]. ...

    Abstract In the intricate landscape of human biology, the mechanistic target of rapamycin (mTOR) emerges as a key regulator, orchestrating a vast array of processes in health and disease [...].
    MeSH term(s) Humans ; Signal Transduction ; TOR Serine-Threonine Kinases
    Chemical Substances TOR Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2024-02-23
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25052587
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  6. Article ; Online: Novel Therapeutic Approaches for Colorectal Cancer Treatment.

    Papavassiliou, Athanasios G / Delle Cave, Donatella

    International journal of molecular sciences

    2024  Volume 25, Issue 4

    Abstract: According to GLOBOCAN 2020 data, colorectal cancer (CRC) represents the third most common malignancy and the second most deadly cancer worldwide [ ... ]. ...

    Abstract According to GLOBOCAN 2020 data, colorectal cancer (CRC) represents the third most common malignancy and the second most deadly cancer worldwide [...].
    MeSH term(s) Humans ; Neoplasms, Second Primary ; Colorectal Neoplasms/drug therapy
    Language English
    Publishing date 2024-02-13
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25042228
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  7. Article ; Online: Mechanotransduction Circuits in Human Pathobiology.

    Gargalionis, Antonios N / Papavassiliou, Kostas A / Papavassiliou, Athanasios G

    International journal of molecular sciences

    2024  Volume 25, Issue 7

    Abstract: It is widely acknowledged that mechanical forces exerted throughout the human body are critical for cellular and tissue homeostasis [ ... ]. ...

    Abstract It is widely acknowledged that mechanical forces exerted throughout the human body are critical for cellular and tissue homeostasis [...].
    MeSH term(s) Humans ; Mechanotransduction, Cellular
    Language English
    Publishing date 2024-03-29
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25073816
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  8. Article ; Online: YAP/TAZ-TEAD signalling axis: A new therapeutic target in malignant pleural mesothelioma.

    Papavassiliou, Kostas A / Sofianidi, Amalia A / Papavassiliou, Athanasios G

    Journal of cellular and molecular medicine

    2024  Volume 28, Issue 8, Page(s) e18330

    Abstract: The Hippo signalling pathway, a highly conserved signalling cassette, regulates organ size by controlling cell growth, apoptosis and stem cell self-renewal. The tumourigenic potential of this pathway is largely attributed to the activity of YAP/TAZ, ... ...

    Abstract The Hippo signalling pathway, a highly conserved signalling cassette, regulates organ size by controlling cell growth, apoptosis and stem cell self-renewal. The tumourigenic potential of this pathway is largely attributed to the activity of YAP/TAZ, which activate the TEAD1-4 transcription factors, leading to the expression of genes involved in cell proliferation and suppression of cell death. Aberrant regulation of the YAP/TAZ-TEAD signalling axis is commonly observed in malignant pleural mesothelioma (MPM), an insidious neoplasm of the pleural tissue that lines the chest cavity and covers the lungs with poor prognosis. Given the limited effectiveness of current treatments, targeting the YAP/TAZ-TEAD signalling cascade has emerged as a promising therapeutic strategy in MPM. Several inhibitors of the YAP/TAZ-TEAD signalling axis are presently undergoing clinical development, with the goal of advancing them to clinical use in the near future.
    MeSH term(s) Humans ; Mesothelioma, Malignant ; Signal Transduction/genetics ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Neoplasms ; Hippo Signaling Pathway
    Chemical Substances Transcription Factors
    Language English
    Publishing date 2024-04-12
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2074559-X
    ISSN 1582-4934 ; 1582-4934 ; 1582-1838
    ISSN (online) 1582-4934
    ISSN 1582-4934 ; 1582-1838
    DOI 10.1111/jcmm.18330
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    Zs.A 5752: Show issues Location:
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  9. Article ; Online: Many faces, many places: delving deeper into CAF heterogeneity in NSCLC.

    Papavassiliou, Kostas A / Adamopoulos, Christos / Papavassiliou, Athanasios G

    Trends in cancer

    2024  Volume 10, Issue 4, Page(s) 277–279

    Abstract: In a recent study published in Cancer Cell, Cords et al. employed multiplexed imaging mass cytometry to analyze cancer-associated fibroblast (CAF) heterogeneity in 1070 NSCLC patients. This work defined good and poor prognostic CAF phenotypes, the latter ...

    Abstract In a recent study published in Cancer Cell, Cords et al. employed multiplexed imaging mass cytometry to analyze cancer-associated fibroblast (CAF) heterogeneity in 1070 NSCLC patients. This work defined good and poor prognostic CAF phenotypes, the latter associated with metastasis and chemoresistance, as well as revealed that CAF spatial location correlates with immune cell infiltration and clinical outcome.
    MeSH term(s) Humans ; Cancer-Associated Fibroblasts/pathology ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Prognosis ; Phenotype ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology
    Language English
    Publishing date 2024-02-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2852626-0
    ISSN 2405-8025 ; 2405-8033 ; 2405-8033
    ISSN (online) 2405-8025 ; 2405-8033
    ISSN 2405-8033
    DOI 10.1016/j.trecan.2024.02.004
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  10. Article ; Online: Malolactone strikes: K-Ras-G12D's Achilles' heel.

    Adamopoulos, Christos / Papavassiliou, Kostas A / Papavassiliou, Athanasios G

    Trends in pharmacological sciences

    2024  

    Abstract: In a recent study in Nature Chemical Biology, Zheng et al. exploiting strain release by malolactone-based electrophiles and designed a first-in-class covalent inhibitor that targets the elusive aspartate of the Kirsten rat sarcoma viral oncogene homolog ( ...

    Abstract In a recent study in Nature Chemical Biology, Zheng et al. exploiting strain release by malolactone-based electrophiles and designed a first-in-class covalent inhibitor that targets the elusive aspartate of the Kirsten rat sarcoma viral oncogene homolog (K-Ras)-G12D variant, which is highly prevalent in pancreatic cancer. The compound drastically inhibited oncogenic signaling and tumor growth in preclinical K-Ras-G12D-mutant pancreatic cancer models, expanding treatment potential beyond K-Ras-G12C-targeted therapies.
    Language English
    Publishing date 2024-04-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 282846-7
    ISSN 1873-3735 ; 0165-6147
    ISSN (online) 1873-3735
    ISSN 0165-6147
    DOI 10.1016/j.tips.2024.04.001
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