P1, N=13, Terminated, Mayo Clinic | N=25 --> 13 | Trial completion date: Dec 2026 --> Jun 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Nov 2024; Financial issues

P1, N=25, Active, not recruiting, Mayo Clinic | Recruiting --> Active, not recruiting

In preclinical models, the postbiotics tyramine could reverse the MAP3K1 mutation-induced MHC-I reduction, thereby augmenting the efficacy of immunotherapy. Collectively, our study identified the vital biomarker driving the immunological heterogeneity of HR+/HER2- breast cancer and elucidated the underlying molecular mechanisms, which provided the promise of tyramine as a novel therapeutic strategy to enhance the efficacy of immunotherapy.

MAP3K1 was correlated with the immune infiltration in glioma. MAP3K1 could facilitate the migration and TMZ resistance of GBM cells through MEK/ERK signalling.

Two years following this, positron emission tomography-computed tomography (PET/CT) revealed multiple masses in both kidneys without other distant metastases, and ultrasonography-guided puncture biopsy indicated the presence of metastatic lung adenocarcinoma. The NGS of both the primary and metastatic lesions revealed the co-alteration of epidermal growth factor receptor (EGFR), RB transcriptional corepressor 1 (RB1), and mitogen-activated protein kinase kinase 1 (MAP3K1), which is potentially associated with the risk of renal metastasis in early postoperative non-small cell lung cancer.

Additionally, inactivating PPP2R3C mutations and activating MAP3K1 mutations both cause congenital syndromes characterized by gonadal dysgenesis.22,23,24,25,26,27,28 As a syndromic PPP2R3C variant is defective in centriolar localization and binding to centriolar protein FOP, we propose that imbalanced activity of this centrosomal kinase-phosphatase pair is the shared cause of these disorders. Thus, our findings reveal a new centrosomal phospho-regulatory module, shed light on disorders of gonadal development, and illustrate the power of systems genetics to identify previously unrecognized gene functions.

P1, N=25, Recruiting, Mayo Clinic | N=18 --> 25 | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

Our findings support the hypothesis that CRC onset may be oligogenic and molecularly heterogeneous. Larger and more robust studies are needed to understand the genetic basis of early-onset CRC development, combined with novel functional analyses and omics approaches.

Our results indicate that the overexpression of MAP3K1 plays a major role in the poor prognosis of HR-positive, HER2-negative early stage breast cancer.

Furthermore, the effect of ASPA (100 μg/mL) on the sensitivity of HCC cells to chemotherapeutic agents, including doxorubicin and cisplatin, was evaluated. In vivo results displayed that ASPA substantially curbed tumor growth and inactivated the MEKK1/NF-κB pathway in mice. All over, ASPA exerts antitumor effects in HCC by suppressing the MEKK1/NF-κB pathway.

Further, GR protein levels were significantly decreased in JNK inhibitor (JNKi, SP600125) treated cells whereas MG132 treatment restored GR levels indicating that DEX induced JNK activity regulated the GR protein levels through proteasomal-degradation pathway. In line with these in vitro data, patient dataset analysis also shows that increased levels of both JNK and GR contributes towards better prognosis of NSCLC patients. Taken together, our data shows that DEX treatment may lead to positive feedback regulation of GR by activating JNK and thus highlights importance of GR-JNK crosstalk in NSCLC.