MAP2K1 (Mitogen-activated protein kinase kinase 1)

Our studies uncover the developmental origins and molecular mechanisms underlying GLI2-amplified SHH-MB. We also reveal that the MAPK pathway plays a critical role in GLI2-driven SHH-MB tumorigenesis and progression.

We found multiple immune suppressive markers were enriched in the endosteum, including Foxp3, CD163, CD27, Pd-1, and Pd-l1, while proliferation markers were enriched in tumor cells in the marrow, including p38 Mapk, pan-Ras, Mek1, and phospho-Erk1/2. These findings shed light on the niche-specific proteins and pathways that are activated in breast cancer bone metastases and establish a user-friendly highly multiplexed approach for spatial proteomics in pre-clinical models of bone metastasis.

Mixed and mixed-feature carcinomas share origins with pure endometrial serous and endometrioid carcinoma subtypes but exhibit distinct molecular alterations. These findings highlight the importance of molecular subtyping for diagnosis and treatment planning. Future research could focus on larger cohorts and targeted sequencing to better understand the pathogenesis of mixed and mixed-feature carcinomas in order to refine therapeutic strategies.

Our data advance the understanding of MAPK signalling and provide a starting point for drug development. Cryo-EM structures of the MEK1-ERK2 complex reveal details of cellular signal transmission.

A few were predicted to be carcinogenic, immunotoxic, and/or cytotoxic. Overall, the clerodane-type furano-diterpenoids from T. crispa show encouraging results in in-silico studies and may be considered for further modification and lead development.

P2, N=150, Not yet recruiting, Gruppo Oncologico Italia Meridionale

Notably, the inhibitory effect of CL-E on STAT3 Tyr705 phosphorylation was reversed by MEK1/2 (U0126) or PKC inhibitors (bisindolylmaleimide II), indicating that CL-E modulates STAT3 signaling through an ERK-mediated mechanism. Collectively, these in vitro findings identify C. longa leaves as an underutilized botanical resource with the potential to regulate IL-6/STAT3 signaling, warranting in vivo evaluation to establish its efficacy, safety and pharmacokinetics, and to define potential therapeutic utility in IL-6/STAT3-driven conditions.

RNA-Seq analysis combined with immunoblotting showed that GLS knockdown reduced the TGF-β, p-Smad2/3, p-p38MAPK, p-ERK1/2, and p-MEK1/2 proteins, increased ROS and glutamine levels in both KYSE30 and KYSE150 cells. Overall, our study showed that GLS promoted the malignant progression via the TGF-β signaling pathway, suggesting that GLS can be a potential therapeutic target and diagnostic biomarker for ESCC.

In this report, we describe 2 rare cases of RDD that underwent sarcomatous transformation and harbored MAP2K1 mutations, both of which demonstrated poor responses to multiple lines of therapy. Additionally, we review 3 other similar cases from the literature.

Its clinical mimicry of vasculitis and other inflammatory disorders can obscure the underlying neoplastic process, delaying diagnosis and access to effective treatment. In patients with systemic inflammation and inconclusive serology, early consideration of Erdheim-Chester disease is essential to guide appropriate investigations and timely therapy.

This international study identifies recurrent IM driver genes, IM-specific mutational signatures, and alterations in IM-associated immune landscapes and microbiomes. Our results highlight a role for nonepithelial somatic alterations (CH) in IM progression to gastric cancer, offering new translational opportunities for early cancer detection and interception.

P2, N=59, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027