Here, we investigated the role of SCAMP3 in ERK1/2 signaling and therapeutic response using TMT-based LC-MS/MS phosphoproteomics of wild-type (WT) and SCAMP3 knockout (SC3KO) SUM-149 cells under basal conditions, after epidermal growth factor (EGF) stimulation, and during ERK1/2 inhibition with MK-8353...These findings position SCAMP3 as a central coordinator of ERK signaling and autophagy. Our results support SCAMP3 as a potential therapeutic target to enhance ERK1/2 inhibitor clinical efficacy and overcome adaptive resistance mechanisms in TNBC.

Our findings establish RAD21-mediated epigenetic regulation as a novel mechanism driving LUAD progression. The efficacy of ulixertinib in suppressing cancer metastasis in preclinical models highlights its translational potential for LUAD therapy.

We screened datasets associated with Gilteritinib and Quizartinib in the Gene Expression Omnibus (GEO) database for enrichment analysis and validated potential key pathways that may limit their therapeutic efficacy through qPCR and Western blot. Transcriptome sequencing revealed that these synergistic effects may stem from the regulation of gene expression such as PKD1, NR2E3, KDF1, and PRSS8 as well as modulation of ion channel activity. This in vitro study identifies aberrant activation of the RAS/MAPK pathway as a critical factor limiting the efficacy of FLT3 inhibitors in FLT3-ITD-positive AML and demonstrates the potent synergistic effects of Ulixertinib combined with FLT3 inhibitors in FLT3-ITD-positive AML cells, providing a novel therapeutic strategy for AML.

P1, N=45, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial primary completion date: Aug 2025 --> Jul 2026

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Dec 2025 --> Dec 2026 | Trial completion date: Dec 2025 --> Dec 2026

P1, N=71, Suspended, JS InnoPharm, LLC | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Dec 2025

The results of the present study showed significantly higher fluorescence intensity of miRNAs 106a-5p and 375-3p, and lower immunoreactivity and the expression of genes encoding ERK1/2, p38, β-catenin and E-cadherin in prostate cancer compared to BPH. It is possible that thanks to miRNA 106a-5p and 375-3p, the proteins we studied belonging to the MAPK and Wnt/β-catenin pathways play a protective suppressor role in prostate cancer cells.

This study identifies a novel MSC-mediated resistance mechanism in which MSC-derived HGF activates compensatory AKT/ERK1/2 signaling, circumventing EGFR blockade by erlotinib. Concurrent upregulation of OPN in NSCLC cells forms a synergistic survival axis under erlotinib pressure. These findings suggest that targeting MSC-derived HGF and tumor-derived OPN may offer promising strategies to overcome erlotinib resistance in NSCLC.

The combined effects of elevated EGR1 expression, along with signaling pathways activated by KRAS and mutant p53, significantly enhance pro-metastatic traits in cancer cells. These findings provide crucial insights into the co-enrichment of KRAS and p53 mutations and pave the way for novel therapeutic strategies targeting this interaction.

Imatinib and N-acetylcysteine (NAC, an antioxidant) attenuated these post-SE events and CA1 neuronal death. However, GPx1 knockdown deteriorated SE-induced CA1 neuronal degeneration accompanied by augmenting c-Abl Y245 phosphorylation and mitochondrial elongation in CA1 neurons. These findings indicate that the impaired reciprocal regulation between c-Abl and GPx1 may cause CA1 neuronal degeneration in response to oxidative stress by abrogating ERK1/2-DRP1-mediated mitochondrial fission.

P1/2, N=192, Completed, Taiho Oncology, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Mar 2025

P1, N=60, Active, not recruiting, D3 Bio (Wuxi) Co., Ltd | Recruiting --> Active, not recruiting