Blog of Signaling Pathways

CRISPR screening identifies mechanisms of resistance to KRASG12C and SHP2 inhibitor combinations in non-small cell lung cancer

53 views | Jan 23 2024

The study uncovers that while KRASG12C inhibitors initially exhibit promising responses, combining them with SHP2, PI3K, and CDK4/6 inhibitors extends regression in preclinical models, yet resistance emerges via KRASG12C amplification and MAPK/PI3K pathway alterations, with FGFR1 loss sensitizing and PTEN loss rescuing against the KRASG12C/SHP2 inhibition. [Read the Full Post]

Chemical Inhibition of ENL/AF9 YEATS Domains in Acute Leukemia

12 views | Jan 23 2024

The research underscores the potential of inhibiting the ENL YEATS domain with SR-0813 as a targeted approach to disrupt the pathogenic function of ENL in acute leukemia while providing the first thoroughly characterized chemical probe for this domain. [Read the Full Post]

Isolinderalactone Induces Apoptosis, Autophagy, Cell Cycle Arrest and MAPK Activation through ROS-Mediated Signaling in Colorectal Cancer Cell Lines

75 views | Jan 23 2024

Isolinderalactone demonstrates significant potential as a therapeutic agent for colorectal cancer by inducing G2/M phase arrest, apoptosis, autophagy, and MAPK pathway activation via ROS-mediated signaling in human CRC cells. [Read the Full Post]

Absorption, Metabolism, and Excretion of [14C]-Tolebrutinib After Oral Administration in Humans, Contribution of the Metabolites to Pharmacological Activity

24 views | Jan 23 2024

The study on tolebrutinib revealed extensive metabolism generating multiple metabolites, among which metabolite M2, constituting 4% of circulating radioactivity, retained potent inhibition of Bruton's tyrosine kinase akin to the parent compound, suggesting its likely contribution to the drug's pharmacological activity in vivo. [Read the Full Post]

Trastuzumab Deruxtecan in Previously Treated Patients With HER2-Positive Metastatic Breast Cancer: Updated Survival Results From a Phase 2 Trial (DESTINY-Breast01)

26 views | Jan 23 2024

The updated analysis of the DESTINY-Breast01 trial underscores the sustained efficacy and generally consistent safety profile of trastuzumab deruxtecan in heavily pretreated patients with HER2-positive metastatic breast cancer, revealing a 62.0% objective response rate, a median overall survival of 29.1 months, and notable treatment-emergent adverse events such as drug-related interstitial lung disease/pneumonitis in 15.8% of patients. [Read the Full Post]

The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity

19 views | Jan 22 2024

The discovery of ABBV-CLS-484 (AC484), a first-in-class active-site inhibitor of PTPN2 and PTPN1, showcases a promising new direction in cancer immunotherapy by enhancing immune response and generating potent anti-tumour effects in preclinical models, offering hope for overcoming resistance to existing treatments. [Read the Full Post]

Covid-19 co-infection with Crimean Congo haemorrhagic fever (CCHF) in a CCHF endemic country: a case report

56 views | Jan 22 2024

In regions where both Crimean-Congo hemorrhagic fever and severe COVID-19 coexist, differentiating between the two diseases is vital due to their overlapping clinical presentations, emphasizing the importance of accurate diagnostic testing to guide appropriate treatment strategies. [Read the Full Post]

Chaetocin-mediated SUV39H1 inhibition targets stemness and oncogenic networks of diffuse midline gliomas and synergizes with ONC201

78 views | Jan 22 2024

Targeting the SUV39H1-H3K9me3 pathway in DIPG cells with chaetocin, and combining it with a DRD2 antagonist like ONC201, presents a promising strategy for effective treatment by exploiting vulnerabilities and overcoming resistance mechanisms. [Read the Full Post]

Inhibitors of the ATPase p97/VCP: From basic research to clinical applications

0 views | Jan 22 2024

In this review, the focus lies on the development and evolution of various p97 inhibitors, notably ATPase inhibitors like CB-5083 and CB-5339, which have exhibited potent anti-tumor activity across diverse models, offering a promising approach for cancer therapy by targeting protein degradation pathways. [Read the Full Post]

PPARα activation promotes liver progenitor cell-mediated liver regeneration by suppressing YAP signaling in zebrafish

9 views | Jan 22 2024

Activation of PPARα and subsequent suppression of YAP signaling promote liver progenitor cell differentiation into hepatocytes, offering potential therapeutic insights for chronic liver disease treatment. [Read the Full Post]

PR-957 retards rheumatoid arthritis progression and inflammation by inhibiting LMP7-mediated CD4+ T cell imbalance

47 views | Jan 21 2024

PR-957 demonstrates potential in alleviating rheumatoid arthritis by targeting LMP7-mediated CD4+ T cell imbalances, offering a promising avenue for therapeutic intervention. [Read the Full Post]

Contribution of Telomere Length to Systemic Sclerosis Onset: A Mendelian Randomization Study

56 views | Jan 21 2024

The study utilizing Mendelian randomization suggests a causal link between longer leukocyte telomere length and a reduced risk of systemic sclerosis, implicating the influence of specific genetic variants in TERC and TERT genes. [Read the Full Post]

Astragalus polysaccharide ameliorates insulin resistance in HepG2 cells through activating the STAT5/IGF-1 pathway

75 views | Jan 21 2024

Astragalus polysaccharide alleviates insulin resistance in HepG2 cells by activating the STAT5/IGF-1 pathway, as evidenced by its restoration of impaired glucose uptake and modulation of IGF-1, IGF-1 receptor, AKT, and STAT5 signaling, findings reinforced by the counteraction of its effects by the STAT5 inhibitor AG490. [Read the Full Post]

Synthesis and structure-activity relationship of new nicotinamide phosphoribosyltransferase inhibitors with antitumor activity on solid and haematological cancer

29 views | Jan 21 2024

The synthesized compounds, particularly 35a, 39a, and 47, exhibit potent nanomolar/sub-nanomolar cytotoxicity against a range of cancer cell lines, showcasing promising anti-cancer potential via NAMPT inhibition and subsequent disruption of the NAD+ pathway, leading to cell death. [Read the Full Post]

Fanconi anemia repair pathway dysfunction, a potential therapeutic target in lung cancer

29 views | Jan 21 2024

Identifying DNA repair deficiencies in lung cancer through the FATSI method may pave the way for tailored treatments targeting specific vulnerabilities, potentially revolutionizing therapeutic strategies for a subset of patients. [Read the Full Post]

A pro-death autophagy-based nanoplatform for enhancing antitumour efficacy with improved immune responses

25 views | Jan 20 2024

The innovative CS-3BP/PA@DOX nanoplatform demonstrates promising potential by leveraging pro-death autophagy, immune modulation, and chemotherapeutic strategies to comprehensively target the tumor microenvironment and enhance anti-tumor efficacy while offering a new therapeutic direction through 3-bromopyruvic acid (3BP) in cancer treatment. [Read the Full Post]

PCDH1, a poor prognostic biomarker and potential target for pancreatic adenocarcinoma metastatic therapy

38 views | Jan 20 2024

The study highlights protocadherin 1 (PCDH1) as a pivotal prognostic biomarker and metastasis promoter in pancreatic adenocarcinoma (PAAD), suggesting flutamide's potential as a therapeutic avenue by down-regulating PCDH1 expression to impede PAAD progression. [Read the Full Post]

Exosomes from PYCR1 knockdown bone marrow mesenchymal stem inhibits aerobic glycolysis and the growth of bladder cancer cells via regulation of the EGFR/PI3K/AKT pathway

29 views | Jan 20 2024

The study demonstrates that bone marrow mesenchymal stem cell-derived exosomes loaded with si-PYCR1 suppress aerobic glycolysis and bladder cancer growth via the PI3K/AKT pathway by targeting EGFR, showcasing a promising therapeutic avenue for the disease. [Read the Full Post]

Regulation of the integrin αVβ3- actin filaments axis in early osteogenic differentiation of human mesenchymal stem cells under cyclic tensile stress

25 views | Jan 20 2024

Cyclic tensile stress influences early osteogenesis in human mesenchymal stem cells through the integrin αVβ3-actin filaments axis while involving nuclear localization of YAP. [Read the Full Post]

Discovery of a highly potent, selective, orally bioavailable inhibitor of KAT6A/B histone acetyltransferases with efficacy against KAT6A-high ER+ breast cancer

25 views | Jan 20 2024

CTx-648, a highly potent and selective KAT6A/KAT6B inhibitor, demonstrates significant anti-tumor activity in ER-positive breast cancer models, including those resistant to endocrine therapy, showing promise for targeting KAT6A in this context. [Read the Full Post]