This study reveals the potent antitumor activity of BVD-523 against thyroid cancer cells bearing MAPK-activating mutations, offering promise for treating aggressive forms of thyroid cancer.

ERK inhibition with ulixertinib (BVD-523) did not demonstrate activity in patients with metastatic uveal melanoma. The toxicities observed were consistent with what would be expected with MAPK pathway inhibition.

Silvestrol inhibits the proliferation of NPC cells by targeting ERK phosphorylation. However, the inhibition of NPC cell migration by silvestrol was independent of the Raf-MEK-ERK pathway. RAP1A, HK2, and GADD45A may be potential targets for the action of silvestrol.

P1, N=211, Recruiting, Antengene Therapeutics Limited | Trial completion date: Dec 2024 --> Jun 2024 | Trial primary completion date: Jul 2024 --> Feb 2024

P1, N=211, Recruiting, Antengene Therapeutics Limited | Trial completion date: Aug 2023 --> Dec 2024 | Trial primary completion date: May 2023 --> Jul 2024

P1, N=50, Recruiting, Nader Sanai | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=27, Recruiting, M.D. Anderson Cancer Center | Suspended --> Recruiting

P1/2, N=220, Recruiting, Ipsen | Not yet recruiting --> Recruiting

P1, N=18, Completed, University of Utah | Active, not recruiting --> Completed

These findings suggest that iron-independent lipid peroxidation due to GPx4 disruption induced cell death via the activation of MEK1/ERK2 as a downstream signal of lipid peroxidation in Tamoxifen-treated ETK1 cells. This indicates that GPx4 gene disruption induces slow cell death and involves a different pathway from RSL3- and erastin-induced ferroptosis in ETK1 cells.

P1/2, N=110, Recruiting, Suzhou Genhouse Bio Co., Ltd.

P1/2, N=220, Not yet recruiting, Ipsen

Elevating MAPK1 rescued circ-LDLRAD3 knockdown-allowed obstruction of PTC cell growth. In conclusion, circ-LDLRAD3 stimulates PTC development by releasing miR-655-3p-targeted MAPK1.

P1/2, N=102, Active, not recruiting, Erasca, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2 | N=200 --> 102

P1/2, N=36, Not yet recruiting, M.D. Anderson Cancer Center

P2, N=52, Completed, Kimberly Perez, MD | Active, not recruiting --> Completed

Molecular docking data demonstrates that CAPE shows a higher docking score of -5.35 versus -4.59 to known p38 inhibitor SB203580 as well as a docking score of -4.17 versus -3.86 to known ERK1/2 inhibitor AZD0364...These results suggest that stress induction via serum starvation in HT29 CRC cells leads to the induction of apoptosis and co-ordinated activation of MAPK-HSP pathways. Molecular docking studies support that CAPE could serve as an effective inhibitor to target p38 and MAPK compared to their currently known inhibitors.

P2, N=101, Terminated, BioMed Valley Discoveries, Inc | Active, not recruiting --> Terminated; Enrollment challenges

P2, N=215, Recruiting, BioMed Valley Discoveries, Inc | Trial completion date: Jun 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Dec 2024

P1, N=71, Suspended, JS InnoPharm, LLC | N=124 --> 71 | Trial primary completion date: Dec 2023 --> Jun 2024

P2, N=16, Terminated, Anita Turk | N=35 --> 16 | Trial completion date: Jul 2024 --> Aug 2023 | Recruiting --> Terminated | Trial primary completion date: Jun 2024 --> Aug 2023; Lack of efficacy.

P1, N=27, Suspended, M.D. Anderson Cancer Center | Phase classification: P1b --> P1 | Not yet recruiting --> Suspended

P1/2, N=42, Suspended, M.D. Anderson Cancer Center | Phase classification: P1b/2a --> P1/2 | Not yet recruiting --> Suspended

P1/2, N=42, Suspended, M.D. Anderson Cancer Center

P1, N=60, Recruiting, JS InnoPharm, LLC

Our findings indicate that ROS, especially HO, are associated with the regulation of ERK1/2 phosphorylation in colon cancer by either increasing or decreasing kinase activity. These data suggest that ERK2 has a growth-promoting role and ERK1 has a regulatory role in colon tumorigenesis, which could lead to new avenues in the development of cancer therapy.

P1/2, N=46, Active, not recruiting, M.D. Anderson Cancer Center | Phase classification: P1b/2 --> P1/2

Circ_FNDC3B downregulation impeded the development of ESCC via the mediation of miR-136-5p/MAPK1 axis. This report afforded a novel insight into the functional mechanism of circ_FNDC3B in ESCC.

Thus, the METTL3/IGF2BP3/circPSMA7/miR-128-3p/MAPK1 axis plays a critical role in BCa progression. Furthermore, circPSMA7 may be a potential diagnostic biomarker and novel therapeutic target for patients with BCa.

The cause of the development of pleomorphic adenomas may be apoptotic disorder and the activation of the inflammatory process. The examined genes may have potential to be new therapeutic targets for the treatment of pleomorphic adenomas.

Our findings suggest that while MAPK1 expression, might be a promising biomarker for evaluating oncogenic activity in patients suspected of BCa. We were not able to detect a prognostic/diagnostic role for MAPK1 promoter methylation.

Despite limited BBB permeability of LY321, combination LY321 and anti-PD-1 treatment amplifies extracranial immune responses that improve intracranial disease control, highlighting the role of extracranial tumors in driving intracranial response to treatment. Combined ERK and PD-1 inhibition is a promising therapeutic approach, worthy of further investigation for patients with melanoma BM.

P1, N=42, Recruiting, Dana-Farber Cancer Institute | N=30 --> 42

P2, N=52, Active, not recruiting, Kimberly Perez, MD | Recruiting --> Active, not recruiting | Trial primary completion date: Nov 2023 --> Aug 2023

P2, N=20, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2024 --> Mar 2026

Our data showed that MAPK1 can bind to the promoter regions of these target genes to control their transcription as a bidirectional transcription factor, promoting AGS cell motility and invasion. Our research has expanded the understanding of the regulatory roles of MAPK1, enriched our knowledge of transcription factors, and provided novel candidates for cancer therapeutics.

Overall, our results describe the importance of Twist1 in MPNST pathogenesis. Everolimus was also found to be a potential therapeutic drug for MPNSTs.

P1b/2, N=46, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

The energetics of the catalytic reaction is affected for all the variants for both the MAPK proteins. The stability changes and the variation in the enzyme catalysis observed for most of MAPK1/3 variants suggest that a local change in a residue, distant from the catalytic site, may have long-distance effects that reflect globally on enzyme stability and functions.

In our example, the binding of a DRS inhibitor can be prevented by mutating the DRS residue Cys-159 to serine, indicating that this residue is essential for the interaction. Resulting inhibitors from this process can be assessed in cellular and in vivo experiments for inhibition of ERK signaling and can be evaluated as potential cancer drugs.

CDC73 promoted MAPK1 ubiquitination and degradation so that affected MAPK1 level and subsequently led to breast cancer progression, providing a novel therapeutic strategy to combat cancer.