Blog of Signaling Pathways

Comparison of multiple synthetic chondroinductive factors in pellet culture against a TGF-β positive control

107 views | Aug 25 2023

The current study found that, despite the promising potential of CM10, CK2.1, kartogenin, and SM04690 as chondroinductive agents, they did not exhibit higher gene expression of chondrogenic markers compared to the positive control TGF-β3, suggesting the need for further research and identification of new chondroinductive factors. [Read the Full Post]

The BET PROTAC inhibitor dBET6 protects against retinal degeneration and inhibits the cGAS-STING in response to light damage

75 views | Aug 25 2023

The study demonstrates that targeted degradation of BET proteins using dBET6 effectively inhibits the cGAS-STING pathway in reactive retinal macrophages/microglia, providing neuroprotective effects and suggesting a potential therapeutic approach for retinal degenerative diseases. [Read the Full Post]

Comparing how well abrocitinib and dupilumab treat atopic dermatitis signs and symptoms: a plain language summary

37 views | Aug 25 2023

The summary discusses a clinical study that found abrocitinib to be more effective than dupilumab in quickly improving the signs and symptoms of moderate to severe atopic dermatitis (AD) in individuals who did not respond to prescribed topical medications. [Read the Full Post]

Efficacy and safety of abrocitinib for moderate-to-severe atopic dermatitis in adolescents and adults: Meta-analysis

109 views | Aug 25 2023

This meta-analysis suggests that abrocitinib is both safe and effective in treating moderate-to-severe atopic dermatitis in adolescents and adults, with the 200 mg dose showing a greater efficacy compared to the 100 mg dose. [Read the Full Post]

SEOM-GEIS clinical guideline for gastrointestinal stromal tumors (2022)

73 views | Aug 24 2023

The Spanish Society of Medical Oncology (SEOM) and the Spanish Sarcoma Research Group (GEIS) recommend a multidisciplinary approach and centralized management in reference centers for the diagnosis and treatment of gastrointestinal stromal tumor (GIST) patients. [Read the Full Post]

Ripretinib in advanced gastrointestinal stromal tumors: an overview of current evidence and drug approval

39 views | Aug 24 2023

Ripretinib, a switch-control tyrosine kinase inhibitor, has shown promise in targeting both primary and secondary KIT and PDGFRα resistance mutations, making it a valuable therapeutic option in the management of advanced gastrointestinal stromal tumors (GISTs) that have developed resistance to imatinib and other treatments. [Read the Full Post]

Therapeutic inhibition of Mcl-1 blocks cell survival in estrogen receptor-positive breast cancers

99 views | Aug 24 2023

The study revealed that inhibiting Bcl-2 or Bcl-xL in ERα+ breast cancer cells leads to rapid mTOR signaling, which triggers cap-dependent translation of Mcl-1 and contributes to resistance to Bcl-2/Bcl-xL inhibitors, but combined treatment with Mcl-1 or mTOR inhibitors enhances apoptosis and reduces tumor growth. [Read the Full Post]

Exposure-Response Analysis to Assess the Concentration-QTc Relationship of Iberdomide

55 views | Aug 24 2023

The study suggests that iberdomide, at its maximum plasma concentration, does not have a clinically relevant effect on QT interval prolongation. [Read the Full Post]

A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy Subjects

34 views | Aug 24 2023

The phase 1 study demonstrated that hepatic impairment had no clinically significant impact on the pharmacokinetics of iberdomide, supporting the conclusion that no dose adjustment is necessary for patients with hepatic impairment. [Read the Full Post]

Oxidative stress enhances the therapeutic action of a respiratory inhibitor in MYC-driven lymphoma

32 views | Aug 23 2023

The combination of complex I inhibition and high-dose ascorbate demonstrates synergistic anticancer effects in MYC-driven cancers, such as high-grade lymphomas, by inducing oxidative stress and disrupting redox homeostasis. [Read the Full Post]

Intraoperative Fluorescein Angiography Can Efficiently Identify Biomarkers And Guide Surgical Decision Making

36 views | Aug 23 2023

This study presents an efficient method for performing fluorescein angiography during Digitally Assisted Vitreoretinal Surgery, enabling real-time visualization and intervention by modifying the accessory light sources and utilizing digital imaging software. [Read the Full Post]

Structure and RAF family kinase isoform selectivity of type II RAF inhibitors tovorafenib and naporafenib

0 views | Aug 23 2023

Type II RAF inhibitors, such as tovorafenib and naporafenib, exhibit potent inhibitory effects against CRAF but display reduced potency against ARAF, highlighting their potential clinical implications and suggesting a relative sparing of ARAF by multiple drugs in this class. [Read the Full Post]

Initial Evidence for the Efficacy of Naporafenib in Combination With Trametinib in NRAS-Mutant Melanoma: Results From the Expansion Arm of a Phase Ib, Open-Label Study

26 views | Aug 23 2023

The combination therapy of naporafenib and trametinib showed promising preliminary antitumor activity in patients with NRAS-mutant melanoma, with manageable adverse events and ongoing research on prophylactic strategies to address skin-related side effects. [Read the Full Post]

Safety and Efficacy of Bromodomain and Extra-Terminal Inhibitors for the Treatment of Hematological Malignancies and Solid Tumors: A Systematic Study of Clinical Trials

61 views | Aug 23 2023

The evaluation of twelve BET inhibitors in clinical trials for hematological malignancies and solid tumors revealed common hematological and non-hematological adverse events, moderate efficacy rates, and the need for further investigation into dosing schemes and combination therapies to enhance their therapeutic potential. [Read the Full Post]

Precision Targeted Therapy with BLU-667 for RET-Driven Cancers

40 views | Aug 22 2023

BLU-667, a highly potent and selective RET inhibitor, has demonstrated significant inhibition of RET signaling and induced durable clinical responses in patients with RET-altered NSCLC and MTC, validating its potential as a targeted therapy for these cancers. [Read the Full Post]

SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor

16 views | Aug 22 2023

The study reveals that the protein SHP2 plays a critical role in decidualization, influencing the nuclear localization of the progesterone receptor and highlighting its potential involvement in recurrent miscarriage. [Read the Full Post]

CDK9 inhibition induces epigenetic reprogramming revealing strategies to circumvent resistance in lymphoma

65 views | Aug 22 2023

AZD4573, a selective inhibitor of CDK9, demonstrates effectiveness in restricting DLBCL cell growth by inducing transcriptional and epigenetic changes, and its combination with PIM kinase or PI3K inhibitors shows promise in overcoming resistance and reducing tumor progression in DLBCL. [Read the Full Post]

The CDK7 inhibitor CT7001 (Samuraciclib) targets proliferation pathways to inhibit advanced prostate cancer

66 views | Aug 22 2023

The study demonstrates that the CDK7 inhibitor CT7001 shows promising antitumor efficacy in castration-resistant prostate cancer (CRPC), inhibiting cell proliferation, inducing apoptosis, and suppressing androgen receptor (AR) signaling, both as a monotherapy and in combination with the antiandrogen enzalutamide. [Read the Full Post]

Interrogating bromodomain inhibitor resistance in KMT2A-rearranged leukemia through combinatorial CRISPR screens

61 views | Aug 22 2023

The study revealed that deficiency of the SPOP gene leads to significant resistance to BET inhibitors (BETi), and a combination therapy targeting both BET and GSK3 using ABBV-744 and CHIR-98014 showed promise in impeding the progression of KMT2A-rearranged leukemia. [Read the Full Post]

Pulsatilla Saponins Inhibit Experimental Lung Metastasis of Melanoma via Targeting STAT6-Mediated M2 Macrophages Polarization

35 views | Aug 21 2023

Pulsatilla saponins derived from Pulsatilla chinensis effectively suppress tumor progression by inhibiting the polarization of M2 macrophages through the STAT6 signaling pathway, revealing a novel mechanism for their anti-tumor activity. [Read the Full Post]