MAP2K2 (Mitogen-activated protein kinase kinase 2)

Anti-PD-L1 and TGF-β bifunctional fusion proteins are feasible and effective for recurrent cervical cancer through the IL 17 signaling pathway and TGF-β signaling pathways. A novel immune infiltration-based gene signature consisting of PMEPA1, FSTL3, SERPINE1, CXCL1, CXCL8, JUND, and MAP2K2 plays a crucial role in recurrent cervical cancer patients with anti-PD-L1 and TGF-β bifunctional fusion proteins.

BA treatment upregulates PLAU gene expression, but this increased PLAU protein subsequently interacts with and inhibited by BA, leading to downstream pathway suppression. It was concluded it could be served as a promising therapeutic strategy for the treatment of PTC.

In conclusion, F2 has significant antitumor activity. One of its mechanisms of action is to suppress angiogenesis in tumor tissue and surrounding tissues by inhibiting the VEGF/ERK/MAP signaling pathway.

P1, N=31, Not yet recruiting, M.D. Anderson Cancer Center

<b></b> <i>Streptomyces griseoaurantiacus</i> HNF214 from beehives produces quercetin and isoquercetin, exhibiting both antibacterial and anticancer activities, likely via MAPK/ERK pathway inhibition. While promising, further safety and <i>in vivo</i> studies are crucial before therapeutic development.

Quercitrin has the lowest binding energy against MEK-1 (-9.963 kcal/mol), 3-hydroxy-β-sitost-5-en-7-one demonstrated the lowest binding energy to ERK-1 (-10.495 kcal/mol), and rutin was best against MEK-2 with a calculated binding energy value of -9.963 kcal/mol. The binding modes of these compounds are compared with the known inhibitors of the oncoprotein targets that showed similar interactions to key amino acid residues indicating their inhibitory potential and are suggested as promising candidates for melanoma treatment.

Our findings underscore the clinical and genetic diversity of RASopathies in the Indian population and highlight the role of next-generation sequencing in early and accurate diagnosis. While exploratory drug-gene interaction analysis provides hypothesis-generating insights, clinical translation requires rigorous validation in functional studies and clinical trials.

Neoadjuvant SRC or MEK inhibition does not appear to mitigate the EMT response to ADT or influence clinical or pathological outcomes.

However, despite the association of somatic BRAF variants and LCH, individuals with CFC syndrome are not thought to have higher rates of LCH. Here, we report two individuals with CFC syndrome and LCH and review the literature examining this potential association.

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.

Remarkably, pazopanib treatment reversed the bleomycin-induced elevation in transforming growth factor-beta-1 (TGF-β1) and α-smooth muscle actin (α-SMA) levels. Our research highlighted the beneficial role of pazopanib in attenuating bleomycin-elicited lung fibrosis through the suppression of MEKK2 and MEKK3 and the modulation of JNK and P38 cascades.

Targeted NGS revealed MET amplification (2 cases), MET mutation (1 case), NOTCH1 mutations (9 cases), and alterations in MAP2K2, FGFR4, DDR pathway genes (e.g., PMS2, CDK12R44W, RAD51C/D), and chromatin remodeling genes (EZH2, ARID1A). These findings support BPRCC as a distinct subtype of papillary RCC with consistent biphasic morphology, immunophenotypic divergence, and a unique molecular profile enriched for NOTCH, MAPK, and DDR pathway alterations.