In this prospective case series selumetinib appeared to be a useful drug for the treatment of PNs.

Moreover, MEK inhibitor (AZD-6244) intervention studies confirmed that CPT inhibits EMT by targeting the MEK pathway...Our results demonstrated that CPT modulates breast cancer migration and invasion via the MEK/ERK/EMT axis by directly targeting MEK1. Our study provides evidence suggesting that CPT may serve as a potential agent for suppressing breast cancer metastasis.

P1, N=9, Recruiting, Pfizer | Not yet recruiting --> Recruiting

Resistance to RET inhibitors can be acquired through RET copy-number gain and secondary mutations as well as NF1 loss-mediated MAPK pathway activation. This mechanism of resistance can be overcome with dual inhibition of RET and downstream RAS/MAPK signaling, demonstrating clinical potential in RET-mutant MTC.

PTPA promotes oncogene-induced senescence (OIS) in MPM. By preventing OIS, heterozygous PTPA loss may contribute to mesothelial transformation and carboplatin resistance.

P2, N=26, Active, not recruiting, University Health Network, Toronto | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=10, Active, not recruiting, UNICANCER | Trial completion date: Mar 2026 --> Mar 2027

P1, N=124, Recruiting, Pfizer | Trial completion date: Feb 2029 --> Jun 2029

P2, N=25, Recruiting, University of California, San Francisco | Trial completion date: May 2027 --> May 2028 | Trial primary completion date: May 2026 --> May 2027

Importantly, deletion of DRP1 leads to either growth inhibition or re-sensitization to trametinib in resistant lines. These findings suggest DRP1 contributes to drug resistance, and that inhibition of mitochondrial fission might be a promising therapeutic strategy to combat resistance to MAPK and RAS inhibitors.

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.

A lead mAb (mAb7) sensitized tumors to the US Food and Drug Administration-approved MAPK kinase inhibitor trametinib and the KRASG12C inhibitor adagrasib. Moreover, a murinized antibody (Ms-mAb7) improved antitumor immunity in a KrasG12D syngeneic tumor model by enhancing infiltration and activation of cytotoxic immune cells. These findings provide an important advance in the clinical development of PCDH7-targeting antibodies for lung cancer treatment.