The findings reveal a crucial role of XPR1 in PTC progression and prognosis via the BRAF-ERK1/2-P53 signaling pathway, providing potential therapeutic targets for treating PTC.

In conclusion, the present study indicated that LBT could induce cell death of HCC via promotion of DUSP1-mediated ERK1/2 inhibition. These data will help to establish the evidence of LBT to treat HCC.

No abstract available

ERK and AKT signaling and their downstream target genes were regulated by CEACAM6 and thus the treatment with AKT inhibitor capivasertib or ERK inhibitor ulixertinib mitigated the CEACAM6-induced migration. These findings demonstrate that CEACAM6 is crucially involved in gallbladder cancer progression by promoting migration and inhibiting cell adhesion through ERK and AKT signaling providing specific options for treatment of CEACAM6-positive cancers.

P1/2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=36 --> 0 | Initiation date: Jul 2024 --> Jan 2025 | Not yet recruiting --> Withdrawn

Finally, the proliferation, migration, and invasion of NT2/D1 cells simulated by E2 or ESR2 were also blocked by PP2 and U0126. This study provides novel insights into molecular mechanisms of ER in NT2/D1 cells by demonstrating that ER activates rapid responses molecules, including SRC and ERK1/2, which enhance the tumorigenic potential of testicular cancer cells.

HLJDD inhibited PAAD in vitro and in vivo via the modulation of multiple mechanisms, including regulation of PI3K/AKT/mTOR and MAPK/ERK1/2 signaling pathways.

ML models reconfirmed the addition of stromal FOXC1 expression and tumor pERK1-2 to NCCN-IPI score had the highest C-index (0.952) among combinations. Stromal FOXC1 and tumor pERK1-2 were determinants of DLBCL prognosis, whose addition significantly improved prognostic performance of the NCCN-IPI.

P1, N=47, Completed, Hutchmed | Recruiting --> Completed | N=87 --> 47 | Trial completion date: May 2024 --> Feb 2024 | Trial primary completion date: Sep 2023 --> Jan 2024

Cory plays an anti-tumor role in ESCC by regulating EZH2-DUSP5-ERK1/2 signaling pathway. Cory may be promising to be a novel therapy for treating ESCC.

Both naporafenib combinations had acceptable safety profiles. Antitumor activity was limited in patients with NSCLC, despite the observed on-target pharmacodynamic effect.

Most samples with RETN amplifications metastasized to bone and showed high expression of IL-8 (CXCL8) and IL-6 (IL6). Finally, resistin could be considered a prognostic marker for basal triple-negative breast cancer, and we also proposed the possibility that resistin-induced cell migration involves the activation of MAPK in breast cancer cells.

Resistance developed in DUSP6 KO cells, indicating a bypass mechanism. Although targeting ASCL1 remains a challenge, our findings suggest that expression of ASCL1, DUSP6 and low phospho-ERK1/2 identify neuroendocrine lung cancers for which DUSP6 may be a therapeutic target.

We show that pirtobrutinib blocked p-ERK1/2, ERK1/2-driven inflammatory cytokines, and overcame paracrine-mediated resistance in MYD88Mut lymphoma cells expressing mutated BTKCys481. Our results provide important mechanistic insights for the activity of pirtobrutinib in MYD88Mut lymphomas carrying BTKCys481 mutations.

Furthermore, our results demonstrated that LB showed potential anti-Ex20ins cancer activity through suppression of the EGFR and ERK1/2 signaling pathway in Ba/F3 cells bearing two to three amino acid insertion mutations. These findings suggested that LB might be valuable for further investigation as a potential candidate in the treatment of associated diseases.

If summarized, our results prove the contribution of ERK2 in compensating ERK1 loss and vice versa and an evident role of ERK1 in cancer cell invasiveness.

In the initial stage, we collected 6 cases of hip joint soft tissue from normal individuals and 6 cases from OA patients clinically to analyze the differential expression of LGALS9 between normal individuals and OA patients; Subsequently, RNAi technology was used to preliminarily clarify the regulatory role of LGALS9 in an in vitro OA model; Then, lentivirus was used to knock down and overexpress LGALS9, and in vivo and in vitro OA models were constructed. QRT-PCR, western blot, safranin fast green staining (SO), immunofluorescence and other experimental methods were used to quantitatively analyze inflammatory and signaling pathway indicators, further improving the regulatory effect of LGALS9 on inflammation and the pathogenesis of OA.

In agreement, clinical data disclose that high KSR1 expression levels correlate with greater metastatic potential and adverse evolution of mammary tumors. Overall, our results portray both ERK dimerization and KSR1 as essential factors for the regulation of cell motility and mammary tumor dissemination.

Finally, we discovered that AIBP could control the MAPK signaling pathway-involved genes expression, including P-MEK, MEK, c-Myc, P-ERK1/2, and ERK1/2, and that GDC-0994, a specific ERK1/2 inhibitor, could suppress the AIBP overexpression induced cell migration and proliferation abilities. These findings demonstrated that the ERK/MAPK signaling pathway might be stimulated by AIBP in HCC tissues, leading to increased cell invasion, migration, and proliferation. It was hypothesized that AIBP might act as a useful prognostic and diagnostic marker for HCC.

Losartan exhibited dual effects on tongue squamous cell carcinoma cells. Moderate losartan concentrations facilitated cell proliferation, whereas high concentrations induced cytotoxicity in tongue carcinoma cells.

P1/2, N=190, Active, not recruiting, Taiho Oncology, Inc. | N=300 --> 190

Our data illustrate that activation of the MAZ-controlled axis promotes thyroid tumorigenesis. These insights would advance our knowledge of the role of TFs in cancer development and highlight the potential of TFs as future targets for treatments against cancers.

P1/2, N=200, Active, not recruiting, Erasca, Inc. | Phase classification: P1b/2 --> P1/2 | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: May 2024 --> May 2025

P1, N=27, Recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Mar 2026 --> Mar 2028

Mira showed anti-apoptotic activity through inhibition of Bax immunoreactivity and elevation of Bcl2. To summarize, Mira exhibited a hepato-and neuroprotective effect against TAA-induced HE in rats via shielding antioxidant defense and mitigation of the pathological inflammatory and apoptotic axis besides upregulation of neuroprotective signaling pathways.

Further LC-MS/MS results showed the anti-inflammatory and analgesic bio-functions of CI5 depended on its interaction with the Rac-2 protein upstream of ERK1/2 and the inflammatory signaling pathway (ERK1/2/COX-2 axis). In summary, CI5, as a novel natural candidate identified from Cinobufacini injection, showed substantial clinical promise for inflammatory pain treatments.

We also found that the expressed level of cathepsin S decreased under pyrocurzerenone treatment. This study showed that pyrocurzerenone reduced ERK1/2 expression of the proteins and cathepsin S, suggesting that it could be a valuable treatment to inhibit human oral cancer cell metastasis.

Our results identified a precise mechanism underlying ZNF468-induced epigenetic upregulation of VEGF-C in facilitating lymphangiogenesis and lymph node metastasis of ESCC, which might provide a novel prognostic biomarker and potential therapeutic for ESCC patients.

These results suggest that FASN silencing suppressed AR through the ERK 1/2 pathway, which in turn suppressed CRLM.

P1, N=45, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Apr 2026 --> Nov 2026 | Trial primary completion date: Jul 2024 --> Aug 2025

P1, N=36, Terminated, Antengene Therapeutics Limited | N=211 --> 36 | Recruiting --> Terminated; The study was terminated based on the internal need to re-prioritization the whole pipeline and phase 1 portfolio.

P2, N=47, Terminated, BioMed Valley Discoveries, Inc | N=215 --> 47 | Trial completion date: Mar 2025 --> Jul 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2024 --> May 2024; Lack of Enrollment for Remaining Open Baskets

The resistance to osimertinib is significantly influenced by cholesterol biosynthesis, highlighting its pivotal role in this context. AETC can enhance osimertinib sensitivity via ERK/SREBP-2/HMGCR-mediated cholesterol biosynthesis. These results provide a promising therapeutic target and potential treatment option for resistance to osimertinib.

Our results reveal that TGF-β expression is upregulated in NSCLC with EGFR mutations through the EGFR-ERK1/2-p90RSK signaling pathway. High TGF-β expression inhibits the infiltration and anti-tumor function of CD8+ T cells, contributing to the "cold" TME of EGFR-mutated tumors. Blocking TGF-β can reshape the TME and enhance the therapeutic efficacy of anti-PD-1 in EGFR-mutated tumors, which provides a potential combination immunotherapy strategy for advanced NSCLC patients with EGFR mutations.

Additionally, harmine-induced apoptosis in colon cancer cells by regulating the expression of Bcl-2 and Bax. In conclusion, our findings suggest that harmine exerts a significant inhibitory effect on the development of colon cancer cells.

These findings provide new insights into the role of CIB1/PAK1-ERK1/2 signaling in lenvatinib resistance in HCC. Targeting CIB1 and its pathways may be a novel pharmaceutical intervention for the treatment of lenvatinib-resistant HCC.

Finally, with in vivo assay, we found obvious Spry4 up-regulation and VEGF-A, bFGF, ERK1/2 phosphorylation, micro-vessel density marker CD31 expression down-regulation in vivo, respectively. Collectively, these results indicated that miR-1293 knockdown could significantly attenuate LUAD angiogenesis via Spry4-mediated ERK1/2 signaling inhibition, which might be helpful for uncovering more functions of miR-1293 in LUAD and providing experimental basis for possible LUAD therapeutic strategy targeting miR-1293.

TAS102 plus regorafenib is a synergistic drug combination in preclinical models of GI cancer, with regorafenib suppressing TAS102-induced increase in microvessel density and p-ERK as contributing mechanisms. The TAS102 plus regorafenib drug combination may be further tested in gastric and other GI cancers.

Both in vitro and in vivo results confirmed the effect of TB on MPM and unravelled novel targets with translational potential.

Collectively, this study identifies a novel BBR-special SE and established a new epigenetic paradigm, by which BBR regulates autophagy, inhibits proliferation, metastasis, and invasion. It provides a rationale for BBR application as the treatment regime in NPC therapy in future.

Ulixertinib, a novel targeted agent with no previous pediatric data, was successfully evaluated in a national precision medicine basket trial. The pediatric RP2D of ulixertinib is 260 mg/m2/dose orally twice a day. Limited single-agent efficacy was observed in a biomarker-selected cohort of refractory pediatric tumors.

Equally interesting, tizaterkib was shown to decrease the number of CD45- and CD68-positive immune cells in the mouse cochlea following noise exposure. This study suggests that repurposing tizaterkib and the ERK1/2 kinases' inhibition could be a promising strategy for the treatment of NIHL.