P2, N=10, Terminated, Children's Hospital Medical Center, Cincinnati | Completed --> Terminated; Results review of patient data

P1, N=42, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2027 | Trial primary completion date: Mar 2025 --> Mar 2027 | Suspended --> Recruiting

P3, N=153, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: May 2027 --> Jan 2025

A panel of colorectal cancer (CRC) cell lines (n = 10) with varying PI3K and MAPK mutational backgrounds were treated with combinations of 5-Flourouracil (5-FU), radiation, the PI3K inhibitor copanlisib, and/or the MEK inhibitor refametinib, and their effects on proliferation in vitro were measured...Our results suggest that activation of the kinase signalling pathway may modulate PI3K/MEK inhibitor responsiveness in colorectal cancer. Furthermore, the addition of copanlisib to 5-FU chemoradiotherapy resulted in an enhanced anti-proliferative cytotoxic effect compared to 5-FU chemoradiotherapy alone, regardless of the background mutational status, and supports further clinical development of this regimen.

Additionally, in the cell lines where activity was observed, some compounds demonstrated an In vitro inhibitory effect superior to that of the control, paclitaxel...In Gb-d1 cells, compounds 4l and 4p exhibited favorable interactions with mitogen-activated protein kinase (MEK) protein, similar to those observed with the known inhibitor selumetinib. In HeLa cells, compounds 4h and 4g showed activity against dihydrofolate reductase (DHFR) protein, driven by hydrogen bonding interactions and favorable aromatic ring orientations. On the other hand, compounds 4b and 4t exhibited no activity, likely due to unfavorable interactions related to halogen substitutions in the aromatic rings.

Selumetinib provided stability and responses across many pLGG subgroups, and some patients achieved prolonged disease control without additional therapy.

P2, N=50, Recruiting, Emory University | Trial completion date: Jun 2026 --> Sep 2028 | Trial primary completion date: Aug 2025 --> Mar 2028

P3, N=165, Recruiting, National Cancer Institute (NCI) | N=290 --> 165

This study deepens our understanding of treatment response markers and their dynamic changes during neoadjuvant therapy. It underscores the significance of these features, particularly given their early emergence and strong associations with response and recurrence.

P2, N=1, Terminated, National Cancer Institute (NCI) | N=95 --> 1 | Trial completion date: Nov 2026 --> Apr 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Nov 2026 --> Apr 2025; Other - slow accrual

P1, N=25, Active, not recruiting, University of Utah | Recruiting --> Active, not recruiting | N=39 --> 25 | Trial completion date: Jan 2026 --> Mar 2029

P2, N=38, Active, not recruiting, Pfizer | Trial completion date: May 2027 --> Nov 2025 | Trial primary completion date: May 2025 --> Nov 2025

By demonstrating its ability to inhibit osteoclast differentiation and protect articular cartilage, RO could offer a new avenue for disease-modifying treatments in OA. Thus, this paper provides valuable insights into understanding the molecular mechanisms and treatment of OA.

In an 81-year-old woman, osimertinib resumption with reduced doses of dabrafenib and trametinib showed therapeutic efficacy with an acceptable safety profile after osimertinib failure. The present case suggests that under active dose modifications of dabrafenib and trametinib, triple TKI therapy exerts therapeutic effects in elderly patients with osimertinib-resistant EGFR-mutated NSCLC and a BRAF V600E mutation.

Differences in the level of LC3A/B and LC3B proteins between the chloroquine and the 3-methyladenine samples indicate that these drugs inhibit autophagy at different stages. The enhancement of the effect of trametinib by autophagy inhibitors suggests the possibility of combining drugs with anti-cancer potential with modulators of the autophagy process.

Combination binimetinib/crizotinib showed a poor tolerability with no objective responses observed in RASMT advanced CRC patients. EudraCT-Number: 2014-000463 - 40 (20/06/2014: A Sequential Phase I study of MEK1/2 inhibitors PD- 0325901 or Binimetinib combined with cMET inhibitor Crizotinib in RAS Mutant and RAS Wild Type with aberrant c-MET).

P3, N=256, Active, not recruiting, Pfizer | Trial completion date: Jun 2026 --> Dec 2025 | Trial primary completion date: May 2025 --> Sep 2025

Notably, the triple combination of USP7i, MEKi, and anti-PD-1 antibody resulted in durable tumor regression, with effects persisting beyond 80 days after treatment cessation. These findings establish USP7i+MEKi as a promising strategy for targeting NRAS, an 'undruggable' mutation in melanoma, and provide a strong rationale for the clinical development of USP7i plus MEKi as an adjuvant therapy to enhance anti-PD-1 immunotherapy in NRAS mutant melanoma patients.

Notably, a ROS inhibitor, N-acetylcysteine (NAC), attenuates all CI-A-modulated changes. Moreover, the CI-A-triggered annexin V-detected apoptosis and caspase 3/8/9 activations of oral cancer cells were downregulated by PD98059. In conclusion, CI-A induces the oxidative-stress- and ERK-dependent antiproliferative and apoptotic mechanism in oral cancer cells and shows the benefit of non-cytotoxicity to normal cells.

Dr. babovic-vuksanovic has received personal compensation in the range of $500-$4,999 for serving as a USMLE items review with NBME.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

P2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

P2, N=60, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

P2, N=66, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

Molecular docking studies revealed that selumetinib inhibits tumor cell proliferation...These findings provide valuable insights and establish a foundation for further exploration of SUSD3's role in pan-carcinomas. Additionally, they offer novel perspectives and potential targets for the development of innovative therapeutic strategies in cancer treatment.

Importantly, combinational treatment of the mitogen-activated extracellular signal-regulated kinase inhibitor selumetinib and ferroptosis inducer sulfasalazine synergistically suppresses ESSENCE-high CRC in a patient-derived xenograft mouse model. Taken together, these findings demonstrate the crucial role of ESSENCE in mediating CRC progression by regulating CAD stabilization and suggest a therapeutic strategy of targeting the ESSENCE-CAD axis in CRC.

This case underscores the need for personalized approaches in treating AM, especially those with rare molecular alterations like AGK-BRAF fusion. Insights from genomic and immune profiling may inform future therapeutic strategies to overcome resistance and improve outcomes in this challenging melanoma subtype.

This causes the accumulation of DNA damage, ultimately leading to apoptotic cell death. Dual PLK1/MEK inhibition emerges as a promising targeted approach in PDAC.

Notably, the proliferation and viability of cells following treatment with 5-fluorouracil, epidermal growth factor receptor inhibitor and src kinase inhibitor were similar between the cell lines. PD98059 inhibited ERK activation and enhanced E-cadherin expression in conventional culture without affecting spheroidogenesis. These results suggested that soluble E-cadherin may be considered as a biomarker for colorectal cancer, although exogenous E-cadherin might not have a further role in malignant transformation.

P2, N=40, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2025 --> Mar 2026

P=N/A, N=37, Terminated, Alexion Pharmaceuticals, Inc. | N=200 --> 37 | Trial completion date: Jun 2028 --> Nov 2024 | Recruiting --> Terminated | Trial primary completion date: Feb 2028 --> Nov 2024; Sponsor decision.

P1, N=212, Not yet recruiting, Beijing Children's Hospital, Capital Medical University; Beijing Children's Hospital, Capital Medical University

MEK inhibitors may promote the healing of fracture pseudarthroses in children with NF1.

P2, N=9, Completed, Abramson Cancer Center at Penn Medicine | Active, not recruiting --> Completed

P1, N=6, Enrolling by invitation, Second Affiliated Hospital of Wenzhou Medical University

We further demonstrated that the combinatory treatment of trametinib together with PD1 antibody enhances the function of effector T cells, sensitizing tumors with elevated Smyd3 and Shcbp1 signaling to αPD1 treatment. This study advances the understanding of breast tumor progression and provides a new selective strategy for breast cancer patients.

P2, N=96, Recruiting, Oslo University Hospital | Not yet recruiting --> Recruiting | Trial completion date: Aug 2033 --> Aug 2036 | Trial primary completion date: Nov 2028 --> Nov 2033

Treatment with binimetinib rapidly improved the patient's clinical condition...Cobimetinib also proved effective in managing CNS symptoms...In cases of neurological involvement in histiocytosis, lumbar puncture and liquid biopsy can sometime overcome the need for a meningeal biopsy. The molecular characterization of histiocytosis is essential for considering the use of targeted therapy, but the lack of an identified mutation should not preclude the use of anti-MEK therapy.

P1/2, N=96, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

In NF1-LOF tumor cells treated with tovorafenib, increase in phosphorylated-ERK (pERK) was observed at low concentrations, with inhibition of pERK at higher concentrations. When tovorafenib was combined with pimasertib in vitro, synergy was observed in a NF1-LOF embryonal rhabdomyosarcoma PDX model ex vivo and a NF1-LOF MPNST cell line in vitro, suggesting that vertical pathway inhibition is needed in the NF1-LOF mutant setting.