Blog of Signaling Pathways

Loss of VOPP1 Contributes to BET Inhibitor Acquired Resistance in Non-Small Cell Lung Cancer Cells

51 views | Aug 01 2023

This study demonstrates that the loss of VOPP1 leads to the gain of BCL-2, resulting in resistance to BET inhibitors in non-small cell lung cancer, and suggests that combination therapy with BET inhibitors and BCL-2 inhibitors may overcome this resistance. [Read the Full Post]

Successful Treatment and Retreatment With Erdafitinib for a Patient With FGFR3-TACC3 Fusion Squamous NSCLC: A Case Report

119 views | Aug 01 2023

This case report demonstrates the potential efficacy of erdafitinib, an FGFR inhibitor, in achieving disease control and radiographic response in a patient with FGFR3-TACC3 fusion squamous NSCLC, suggesting the need for further investigation and expanding therapeutic options. [Read the Full Post]

Current scenario of pyrazole hybrids with in vivo therapeutic potential against cancers

93 views | Aug 01 2023

This review provides a comprehensive overview of the potential of pyrazole hybrids as anticancer agents, summarizing their mechanisms of action, toxicity, and pharmacokinetics, with the aim of facilitating the rational exploitation and development of more effective candidates for cancer therapy. [Read the Full Post]

Phase 1 pilot study of RRx-001 + nivolumab in patients with advanced metastatic cancer (PRIMETIME)

24 views | Aug 01 2023

The phase 1 pilot study demonstrated that the combination of RRx-001 and nivolumab was well-tolerated, showed preliminary anti-cancer activity, and further clinical trials with this combination are warranted. [Read the Full Post]

Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence

35 views | Jul 31 2023

This literature review examines the risks and safety of combining radiotherapy with anti-HER2 therapies in breast cancer, suggesting that monoclonal antibodies and checkpoint inhibitors can be safely combined with radiation, while caution is warranted for tyrosine kinase inhibitors and antibody-drug conjugates due to limited evidence. [Read the Full Post]

Inducing cathepsin L expression/production, lysosomal activation, and autophagy of human dental pulp cells by dentin bonding agents, camphorquinone and BisGMA and the related mechanisms

52 views | Jul 31 2023

The study found that dentin bonding agents containing camphorquinone (CQ) and bisphenol A-glycidyl methacrylate (BisGMA) stimulated cathepsin L production, lysosomal activity, autophagy, and apoptosis in human dental pulp cells, potentially impacting pulpal changes following tooth restoration. [Read the Full Post]

The effect of the ATM inhibitor AZD0156 on the radiosensitivity of human breast cancer and lung fibroblast cells

58 views | Jul 31 2023

The combination of irradiation and AZD0156 showed enhanced efficacy in inducing cell cycle arrest and reducing clonogenic survival in breast cancer cells, while having minimal effect on fibroblast cells. [Read the Full Post]

ML390 inhibits enterovirus 71 replication by targeting de novo pyrimidine biosynthesis pathway

16 views | Jul 31 2023

ML390, a dihydroorotate dehydrogenase inhibitor, demonstrates potent anti-EV71 activity by inhibiting viral replication through interference with the pyrimidine synthesis pathway, showing potential as a treatment for hand, foot, and mouth disease caused by EV71 infection. [Read the Full Post]

Development of Highly Potent and Selective Pyrazolopyridine Inhibitor of CDK8/19

29 views | Jul 31 2023

JH-XVI-178 (compound 15) is a highly potent and selective inhibitor of CDK8/19 with low clearance and moderate oral pharmacokinetic properties, developed through a hybridization approach starting from CCT251921 and MSC2530818. [Read the Full Post]

Platelet-derived lysophosphatidic acid mediated LPAR1 activation as a therapeutic target for osteosarcoma metastasis

52 views | Jul 30 2023

Targeting the LPA-LPAR1 axis shows promise as a therapeutic intervention for advanced osteosarcoma by inhibiting invasion and metastasis of the cancer cells. [Read the Full Post]

HIF2 Inactivation and Tumor Suppression with a Tumor-Directed RNA-Silencing Drug in Mice and Humans

16 views | Jul 30 2023

This study demonstrated the successful inhibition of HIF2α and tumor suppression using a systemic, tumor-directed, RNA-silencing drug (siHIF2), providing a proof-of-principle for targeted RNA-based therapeutics in clear cell renal cell carcinomas (ccRCC). [Read the Full Post]

Specific HIF-2α (Hypoxia-Inducible Factor-2) Inhibitor PT2385 Mitigates Placental Dysfunction In Vitro and in a Rat Model of Preeclampsia (RUPP)

33 views | Jul 30 2023

The study demonstrates that PT2385, an oral specific HIF-2α inhibitor, shows promise in treating severe placental dysfunction associated with preeclampsia by enhancing cytotrophoblast differentiation, normalizing angiogenic factor secretion, and preventing the onset of maternal symptoms in an animal model. [Read the Full Post]

EZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine

39 views | Jul 30 2023

The study suggests that targeting the EZH2 histone methyltransferase with inhibitors like CPI-1205 and utilizing metformin may hold promise as potential therapeutic options for patients with small intestinal neuroendocrine tumors (SI-NETs). [Read the Full Post]

Sevoflurane induces neurotoxic effects on developing neurons through the WNK1/NKCC1/Ca2+ /Drp-1 signalling pathway

27 views | Jul 30 2023

The study found that sevoflurane-induced neurotoxicity in hippocampal neuronal cells is mediated through the WNK1/NKCC1/Ca2+/Drp-1 signaling pathway, and inhibiting this pathway can alleviate cell viability reduction and apoptosis caused by sevoflurane exposure. [Read the Full Post]

Eganelisib, a First-in-Class PI3K-γ Inhibitor, in Patients with Advanced Solid Tumors: Results of the Phase 1/1b MARIO-1 Trial

19 views | Jul 29 2023

The MAcrophage Reprogramming in Immuno-Oncology-1 (MARIO-1) study evaluated the safety and tolerability of eganelisib as a monotherapy and in combination with nivolumab in patients with solid tumors, with observed toxicities leading to the selection of eganelisib doses of 30 mg and 40 mg once daily for the phase 2 study. [Read the Full Post]

1400 W, a selective inducible nitric oxide synthase inhibitor, mitigates early neuroinflammation and nitrooxidative stress in diisopropylfluorophosphate-induced short-term neurotoxicity rat model

15 views | Jul 29 2023

1400W treatment at 15 mg/kg per day for two weeks significantly reduces DFP-induced nitrooxidative stress, neuroinflammation, and neurodegenerative changes, but does not significantly impact epileptiform spike rate or spontaneous seizures. [Read the Full Post]

UBA1 inhibition contributes radiosensitization of glioblastoma cells via blocking DNA damage repair

60 views | Jul 29 2023

The study demonstrated that the UBA1 inhibitor TAK-243, in combination with ionizing radiation, effectively inhibited GBM cell proliferation, impaired DNA double-strand break repair, and increased apoptosis, providing a potential therapeutic approach to enhance the radiation sensitivity of GBM. [Read the Full Post]

Proteasomal pathway inhibition as a potential therapy for NF2-associated meningioma and schwannoma

39 views | Jul 29 2023

This study highlights the potential of proteasome pathway inhibitors, specifically ixazomib and TAK-243, as novel and promising therapies for NF2-associated tumors, demonstrating efficacy in preclinical models and laying the groundwork for future clinical investigations. [Read the Full Post]

Prototropic forms of hydroxy derivatives of naphthoic acid within deep eutectic solvents

30 views | Jul 29 2023

The prototropic behavior of probes in deep eutectic solvents (DESs) is strongly influenced by the varying hydrogen-bonding capabilities of the DES constituents, as observed through the presence or absence of specific prototropic forms of the probes in different DES compositions. [Read the Full Post]

Thioredoxin-interacting protein deficiency protects against severe acute pancreatitis by suppressing apoptosis signal-regulating kinase 1

49 views | Jul 28 2023

TXNIP, a protein involved in redox reactions and inflammatory responses, plays a significant role in acute pancreatitis by regulating the activation of JNK/p38 pathways and influencing oxidative stress, suggesting its potential as a therapeutic target for protecting against severe acute pancreatitis. [Read the Full Post]