P3, N=510, Recruiting, Jazz Pharmaceuticals | Trial completion date: Aug 2026 --> Jun 2028 | Trial primary completion date: Aug 2026 --> Jun 2028

Combination with the ERK1/2 inhibitor SCH772984 further enhanced efficacy. Collectively, Abrine exerts potent anti-metastatic effects by directly targeting ERK to inhibit MAPK signaling, reversing EMT and engaging the Nrf2/Keap-1/HO-1 pathway, highlighting Abrine alone or with ERK inhibition as a promising therapeutic strategy against lung metastasis model.

To overcome this issue, herein, we developed a cobalt-pheophytin (CoPheo) coordination micelle chelating two chemotherapeutic agents including ONC201 and Palbociclib (Pal), yielding CoPheo-ONC201-Pal-F127. In addition, ONC201-mediated mitogen-activated protein kinase kinase (MEK) inhibition, combined with Pal-induced CDK4/6 blockade, promotes cellular senescence and remodels the tumor microenvironment. These three independent mechanisms collectively establish a mutually enhanced therapeutic strategy capable of overcoming the complex drug resistance driven by multiple downstream signaling pathways in KRAS-mutant pancreatic cancer.

Our results highlight ONC206 as a novel therapeutic option for patients with high-risk medulloblastoma and provide strong rationale for testing the efficacy of ONC206 in the treatment of these patients.

P1, N=42, Completed, Nader Sanai | Active, not recruiting --> Completed | Trial completion date: Feb 2028 --> Sep 2025

P2, N=208, Recruiting, BioVie Inc. | Trial completion date: Jan 2026 --> Aug 2026 | Trial primary completion date: Nov 2025 --> Jun 2026

P2, N=0, Withdrawn, University of Nebraska | N=27 --> 0 | Suspended --> Withdrawn | Trial primary completion date: Apr 2026 --> Apr 2027

P1, N=58, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Jul 2026 --> Jul 2028 | Trial primary completion date: Feb 2026 --> Feb 2028

We propose that concurrent treatment with ONC201 may delay onset of resistance to RAS inhibitor therapy. ClpP activation by dordaviprone/ONC201 suppressed PDAC cell growth and overcame resistance to the RAS(ON) multi-selective inhibitor RMC-7977, providing support for investigating this combination as a potential combination treatment for KRAS-mutant pancreatic cancer.

FAM83A is crucial in the advancement and spread of LUSC, as it promotes EMT and inhibits apoptosis via the activation of the ERK pathway. These findings highlight its potential as a strategic molecular target for the treatment of LUSC.

P1, N=36, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Mar 2026 --> May 2027

Similarly, ERK1/2 inhibition by SCH772984 impairs WED-induced neutrophil differentiation and bactericidal activity, decreasing PU.1 and CEBPβ expression without affecting TLR2 levels. These findings position TLR2 as a key therapeutic target for neutropenia, with WED effectively promoting neutrophil differentiation via TLR2 and MEK/ERK pathway activation. This study highlights the therapeutic potential of targeting TLR2 to alleviate neutropenia and underscores the utility of a multi-omics approach in uncovering drug mechanisms.