In view of pleotropic impact of MAPK, we thought whether MAPK targeting would enhance sensitivity of highly resistant PDAC cells toward gemcitabine...Indeed, in-silico data, corroborating in vitro findings, demonstrated that high expression of p38α (MAPK14) confer poor prognosis and disease-free survival in PDAC patients over p38MAPK low tumor patients. Taken together our data, potentially demonstrated that p38MAPK targeting is potential approach for breaking resistance of PDAC toward chemotherapy and may contribute to controlling PDAC burden effectively.

The cytotoxic effects of three MAPK pathway inhibitors (selumetinib, vemurafenib, dabrafenib) were assessed in ATC cell lines and xenograft models via viability assays and 18F-FDG PET/CT. Furthermore, MAPK pathway inhibitors increased radioiodine uptake in ATC cells. The MAPK pathway inhibitors enhance NIS function through two mechanisms: upregulation of NIS expression and increased ARF4-mediated NIS membrane transport.

FGFR2 is lowly expressed in DFU and can exert a protective effect by activating the PI3K/Akt pathway. It is a candidate diagnostic biomarker and potential therapeutic target for DFU.

P1, N=91, Terminated, Deciphera Pharmaceuticals, LLC | Phase classification: P1/2 --> P1 | N=144 --> 91 | Trial completion date: Aug 2028 --> Mar 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2027 --> Mar 2026; Trial terminated due to business decision, not based on any safety or efficacy concerns.

In vivo, endothelial GPRC5B deficiency significantly accelerated tumor growth and neovascularization, phenotypes that were effectively reversed by the p38 inhibitor SB202190. Clinical specimens corroborated reduced GPRC5B expression and increased microvessel density in MetS-associated PCa. Collectively, our findings establish endothelial GPRC5B downregulation as a key molecular driver promoting pathological angiogenesis via the MKK3/6-DUSP1-p38 axis, suggesting that targeting this signaling cascade offers a promising therapeutic strategy for managing MetS-associated PCa aggression.

The p38 MAPK inhibitor SB202190 reversed ORI-induced effects on cell death, cell migration and invasion, and apoptosis, highlighting the critical role of the p38 MAPK/p53 pathway. ORI effectively suppressed subcutaneous tumour growth in nude mice without notable toxicity while upregulating apoptosis-related proteins Bax and cleaved caspase-3 and downregulating Bcl-2 through activation of the p38 MAPK/p53 pathway.

Therefore, Viscosalactone B and Withasomniferol C are promising natural candidates for further validation as potential MAPK14 inhibitors. In comparison with synthetic drugs like ralimetinib, these plant-derived compounds may offer complementary therapeutic potential with fewer adverse or off-target effects and favorable pharmacokinetic and pharmacophoric profiles.

Pretreatment with the inhibitor SB202190 decreased the expression of proteins related to Ras/Raf/p38 MAPK and significantly suppressed the proliferation, migration, and invasion of A549 cells...NFATc1 is highly expressed in LUAD tissues, and its expression level is closely related to clinical characteristics. NFATc1 may promote the proliferation, migration, and LUAD cell invasion via the Ras/Raf/p38 MAPK pathway, providing a new therapeutic target for LUAD.

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