The mice in the anti-p38MAPK group and the anti-p38MAPK + LV-OPN-0423 group were then given SB202190 (this is an inhibitor of p38MAPK) for 4 weeks, and the mice in each group were injected with corresponding lentivirus diluent once a week for 8 weeks...The OPN level promoted the expression of p38MAPK and p-p38MAPK. These results suggested that OPN could regulate Em's growth and metastasis through the p38MAPK signalling pathway in host hepatocytes, providing evidence that OPN and p38MAPK may be novel molecular targets for treating alveolar echinococcosis.

P1/2, N=144, Active, not recruiting, Deciphera Pharmaceuticals, LLC | Recruiting --> Active, not recruiting

Although ravoxertinib alone showed limited antitumor activity, its combination with BRAFi/MEKi yielded substantial benefits, especially in chronic settings. These findings suggest that combinatorial regimens incorporating ERK inhibitors represent a promising therapeutic strategy for BRAF-mutant melanoma.

P2, N=19, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Sep 2025 --> Sep 2026

Jingui Shenqi pill can exert therapeutic effects on cardiorenal syndrome by inhibiting the activation of the MAPK signaling pathway and inflammatory responses.

The ERK inhibitor GDC-0994 exhibited significant synergistic effects with the AR inhibitor bicalutamide. Specifically, the combination therapy inhibits FOXC2-driven EMT and induces ferroptosis via the FOXC2-Hippo signaling axis, suppressing tumor proliferation, migration, and invasion. In summary, this study uncovers the value of AR/ERK co-targeting in TNBC, which might potentiate the development of novel targeted therapeutic strategies in TNBC.

We find that mouse BrafV600E-driven anaplastic thyroid cancers (ATC) respond markedly to the RAF + MEK inhibitors dabrafenib and trametinib (dab/tram) and that this is associated with upregulation of MhcII in cancer cells and increased CD4+ T-cell infiltration. Moreover, depletion of CD4+, but not CD8+ T-cells, also abrogates response to dab/tram. These findings implicate MHCII-driven CD4+ T cell activation as a key determinant of the response of Braf-mutant ATCs to MAPK inhibition.

Our model showed that both corneal epithelium and fibroblasts synthesize their own estrogen, and β-estradiol treatment via p38 MAP kinase pathway regulates MMP2-mediated collagen fiber degradation. p38 MAP kinase inhibitor SB202190 significantly reduced β-estradiol-induced MMP activity and collagen breakdown, as well as cytokine regulation suggesting a potential therapeutic approach.

Our findings support treatment with BET + BRAF + EGFR inhibitors for patients with BRAFV600E-mutant mCRC [ NCT06102902 ]. This study also highlights the potential of combining epigenetic agents to standard targeted therapy, offering a novel treatment option for this subset of patients.

Furthermore, we demonstrated that targeting ERK1/2 with ravoxertinib (an ERK1/2 inhibitor) could significantly enhance the sensitivity of resistant HCC cells to lenvatinib therapy. Overall, lenvatinib-induced AHR activation promotes AREG expression, which subsequently facilitates the acquisition of drug resistance in HCC via the EGFR-ERK1/2-CyclinD1 signaling axis. Targeting ERK1/2 and AHR effectively improved the response to lenvatinib treatment in resistant HCC.

Concurrently, the combined regimen enhanced their respective anticancer effects by inhibiting the key genes HDAC10 and BCL-xL. Taken together, venetoclax combined with chidamide presents a potent anticancer strategy in preclinical models of t-FL and merits further exploration in clinical trials to validate its effectiveness and safety for treating t-FL.

P2, N=33, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital