In endometrial cancer, dostarlimab combined with chemotherapy improved PFS in both dMMR/MSI-H and mismatch repair-proficient disease and increased OS overall...Confidence is strongest for PD-1 inhibitors in MSI-H/dMMR tumors, trastuzumab deruxtecan in HER2-low or HER2-positive cancers, and encorafenib-based regimens in BRAF V600E metastatic colorectal cancer. Implementation should include validated assays (including reconfirmation of HER2 status), prioritize earlier treatment lines where gains are greatest, and require vigilant ILD monitoring. Head-to-head trials and assay standardization, especially for tumor mutational burden, remain priorities.

Additionally, consistent "Rho GTPase signaling" changes were observed across both proteomic and phosphoproteomic analyses, underscoring the functional reactivation of this pathway in resistant tumors. In summary, these findings reveal molecular signatures of early response and acquired resistance to vemurafenib and offer a valuable resource for future investigation of BRAF-targeted therapy.

These findings suggest that delivering vemurafenib in polymeric nanocapsules produces delayed but sustained cytotoxic and apoptotic effects in ATC cells in vitro, warranting further investigation of this nanocarrier approach for thyroid cancer treatment. Altogether, the biological results reported in this study are derived from in vitro experiments and require further validation in in vivo models.

Furthermore, the combination of vemurafenib with cysmethynil, a proof-of-concept ICMT inhibitor, showed efficacy in combating RAC1P29S-driven resistance of BRAFV600E melanoma cells in both in vitro and in vivo settings...We further validated the role of TAZ in RAC1P29S-driven resistance by demonstrating that introducing a constitutively-active TAZ mutant enhanced the resistance to MAPK pathway inhibitors in native cells, phenocopying the effect of RAC1P29S. The novel application of MAPK pathway inhibitors and cysmethynil combination in RAC1P29S-driven MAPK-pathway-inhibitor-resistant melanoma cells extends the potential utility of ICMT inhibitors, and also provides a new mechanism for targeting ICMT in cancer.

P2, N=7, Terminated, Northwestern University | Trial completion date: Jul 2030 --> Apr 2026 | Active, not recruiting --> Terminated | Trial primary completion date: May 2026 --> Oct 2025; The study was closed due to accrual.

P2, N=28, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=45 --> 28 | Trial completion date: Jul 2028 --> Jun 2029 | Trial primary completion date: Apr 2028 --> May 2026

P2, N=64, Completed, University of Sydney | Active, not recruiting --> Completed

BRAF inhibitors such as encorafenib are ineffective due to MAPK pathway reactivation driven by BRAF dimerization...dHuR abrogated BRAF expression by inducing its exon 18 skipping, and demonstrated superior suppression of BRAF-mutant CRC tumours including those gaining resistance to BRAF inhibitors. Finally, we performed kinome library CRISPR screening and revealed that inactivation of EGFR or MEK enhanced dHuR cytotoxicity, thus establishing a combinatorial strategy to treat patients with refractory BRAF-mutant CRC.

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

P2, N=7, Active, not recruiting, Northwestern University | Recruiting --> Active, not recruiting | N=43 --> 7 | Trial primary completion date: Jul 2028 --> May 2026

P2, N=86, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2026 --> Jun 2027 | Trial primary completion date: Sep 2026 --> Feb 2026