Pharmacological inhibition of FAK with single agent VS-4718 did not significantly reduce macroscopic tumor volume; however, its use in combination with the mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib resulted in both a significant reduction in tumor volume and the preservation of dorsal root ganglion architecture. Our findings establish a critical role for FAK in schwannoma development and provide rationale for evaluation of combination FAK plus MEK inhibition in future clinical trials for NF2-associated SWN.

Encorafenib, cetuximab, and binimetinib are targeted therapies developed for metastatic colorectal cancer with a BRAF V600E mutation. The case highlights the potential use of BRAF V600E targeted therapy in BRAF V600E-mutated duodenal cancer and the importance of molecular profiling in rare cancers. Further research is needed on the effect and safety of targeted therapy for small bowel adenocarcinoma.

IFNG, PTPN6, SLC38A1, and SOCS1 may serve as potential biomarkers of poor prognosis in SKCM patients. These genes demonstrate predictive value for immunotherapy response and drug sensitivity, particularly indicating susceptibility to selumetinib treatment, and therefore show substantial potential for clinical translation.

P1, N=104, Completed, Royal Marsden NHS Foundation Trust | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Oct 2025 | Trial primary completion date: Jun 2025 --> Oct 2025

P2, N=40, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

P1/2, N=16, Active, not recruiting, National Cancer Institute (NCI) | N=58 --> 16 | Trial completion date: Nov 2025 --> Jan 2027

Selumetinib granule formulation (25 mg/m2 dose equivalent, twice a day) had comparable exposure to selumetinib capsule formulation, and was palatable with a manageable safety profile. Selumetinib granule formulation is potentially suitable for young children with NF1-PN who cannot swallow capsules.

P4, N=165, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P2, N=66, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> May 2026 | Trial primary completion date: Jan 2026 --> May 2026

P2, N=25, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

In pre-clinical PC, TIMP-1/CISS proves targetable through combined inhibition of upstream kinases with clinically approved drugs trametinib and nintedanib. Collectively, CISS represents a ubiquitous signature of pro-tumor immunoinstruction with actionable diagnostic and therapeutic potential across human cancers.

The oral drug combination was well tolerated with no dose-limiting toxicity or need for dose reduction over the 4 year period. The Avutometinib and Defactinib combination may represent a new standard treatment option for platinum-resistant and AI-resistant/recurrent LGSOC who have failed other MEKi.