ERK1/2 inhibitors may serve as novel molecular-targeted drugs for treating leukemia with NRAS mutations.

Finally, miR-145-5p inhibits SENP2 transcription, enhances ERK2 SUMOylation, and ultimately suppresses the progression of breast cancer. These revelations suggest evolving ideas for the miR-145-5p-SENP2 axis in therapeutic intervention, thus heralding transformative prospects for the clinical management of breast cancer.

P1, N=111, Terminated, Merck Sharp & Dohme LLC | Completed --> Terminated; business reasons.

In addition, the high expression of model gene produced drug resistance to trametinib, selumetinib and RDEA119 (refametinib). The prognostic risk model based on six prognostic related DEGs is an independent prognostic factor of HCC, which can effectively predict the survival and prognosis of HCC patients.

This study validated the anti-tumor efficacy of Lipo-HNK against NSCLC. Lipo-HNK reduced the infiltration of MDSCs and M2 macrophages by inhibiting the PI3K/Akt pathway and enhanced the therapeutic effects of ICIs. These findings provide evidence and new insights into Lipo-HNK as a promising anti-cancer drug for NSCLC treatment, highlighting its potential to overcome resistance to current ICI therapies.

VAT confers a complex and blended pathogenic transcriptomic profile in obese patients, where abnormal processes are mainly controlled by activating intracellular signaling pathways that exhibit a high degree of redundancy. Identifying shared cross points between those pathways could allow specific targeting treatments to exert a widespread effect over multiple pathogenic processes.

In terms of drug sensitivity, the high-risk group was more sensitive to vinblastine, Acetalax, VX-11e, and PD-0325901, while the low-risk group was more sensitive to Sabutoclax, SB-505124, cisplatin, and erlotinib. The prognostic risk model of ovarian cancer associated to mitochondrial genes built on the basis of public database better evaluated the prognosis of ovarian cancer patients and guided individual treatment.

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.

An untargeted metabolomics study showed that the levels of 4-hydroxyproline, rhamnose, and cysteine were increased after AM supplementation, and their extending effect on the lifespan and health-span of C. elegans were partly dependent on the pmk-1 gene. In conclusion, our results revealed that AM can promote the lifespan and health-span of C. elegans via the PMK-1 pathway, highlighting the potential of AM as a dietary supplement to delay aging.

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

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

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

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.

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

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

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

No abstract available

The findings of this study suggest that SOX4 promotes the phosphorylation modification of IQGAP1 by activating MAPK1 transcription, thereby facilitating the growth and metastasis of pancreatic cancer.

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.

In the high-risk group, erlotinib showed higher IC50 values compared to the low-risk group which exhibited higher IC50 values for VX-11e, AKT inhibitor VIII, AT-7519, BMS345541, Bortezomib, CP466722, FMK, and JNK-9L. The results of RT-qPCR revealed that the expression of four UEGs was higher in tumor tissue as compared to normal tissue. Based on the genes that were expressed differently and associated with ubiquitination-related tumor categorization, we have developed a pattern of four genes and a strong nomogram that can predict the prognosis of HCC, which could be useful in identifying and managing HCC.

We developed a novel Anoikis-related risk score model, which can assist clinicians in evaluating the prognosis of osteosarcoma patients in clinical practice. Analysis of the tumor immune microenvironment and chemotherapeutic drug sensitivity can provide necessary insights into subsequent mechanisms. MAPK1 may be a valuable therapeutic target for neoadjuvant chemotherapy in osteosarcoma.

P1/2, N=46, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

Our study identifies a novel micropeptide AF127577.4-ORF hidden in a lncRNA, with a potent anti-proliferating function in GBM by diminishing METTL3 protein stability by reducing the ERK2/METTL3 interaction. This micropeptide may be beneficial for development of therapeutic strategies against GBM.

P1, N=42, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Apr 2024 --> Apr 2025

P2, N=38, Recruiting, Memorial Sloan Kettering Cancer Center

P1/2, N=300, Active, not recruiting, Astex Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting

Treatment with the neural precursor cell expressed developmentally downregulated protein 8-activating enzyme inhibitor pevonedistat resulted in increased hPRLrL and the death of breast cancer cells. Treatment of breast cancer cells with ERK1/2 inhibitor ulixertinib resulted in decreased colony-forming ability and less proliferation. These studies suggest that the hPRLrI I-tail contributed to breast oncogenesis and may be a promising target for the development of new breast cancer therapies.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI)

Our data suggest that ERK1/ERK2 contribution to BRAFV600E-driven phenotypes is dynamic and varies dependently on cell type, the biological function, and the level of ERK-pathway activation. Our findings also provide useful insights into the comprehension of BRAFV600E-driven malignancies pathophysiology as well as the consequences in vivo of novel ERK pathway-targeted anti-cancer therapies.

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