RAS mutation

Among cases with follow-up data (n=35), all 17 tumors with disease progression were DLL3 positive (13 RET-mutated tumors, 1 RAS-mutated tumor, and 3 RET/RAS wild-type tumors), including 5 with moderate expression and 12 with high expression. Most MTCs express DLL3; moreover, DLL3 expression is associated with lymph node metastases at diagnosis and disease progression, indicating that DLL3 may be an effective therapeutic target in MTC.

BRAF and RAS mutation occurred in 60% and 14% of the patients with available molecular data, respectively. No patients harbored HER2 amplification, suggesting that the co-occurrence of HER2 amplification and dMMR/MSI is essentially anecdotal, making therefore HER2 testing in this subgroup less compelling.

P1/2, N=90, Recruiting, Isofol Medical AB | Trial completion date: Mar 2029 --> Dec 2029 | Trial primary completion date: Mar 2028 --> Nov 2028 | N=60 --> 90

Thermal tumor ablation is a favorable treatment option for patients with RAS-mutated CRLM, particularly for those with tumors of specific size ranges (≤5 cm) and an appropriate tumor burden.

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.

Notably, the mean duration of disease progression following EGFR-TKI initiation did not differ significantly between patients with EGFR exon 21 p.L858R mutation and those with EGFR 19-Del. Our study reveals the heterogeneity of compound EGFR mutations, and characterizes the spectrum of acquired resistance mutations to EGFR TKIs.

These results demonstrate that CKLF is a critical node linking gene copy number changes, oncogenic signaling pathways, and immunophenotypic alterations in hepatocellular carcinoma. Thus, CKLF represents a promising biomarker and therapeutic target for providing individualized therapies to HCC patients.

KRAS G12C mutations represent an independent adverse prognostic biomarker in mCRC, with a statistically significant 28% increased risk of mortality compared to other RAS mutations. The consistent hazard ratio across multiple sensitivity analyses supports a true prognostic effect. These findings have important implications for patient counseling and risk stratification. While the poor prognosis may provide rationale for prioritizing trial enrollment, translation into therapeutic decision-making requires caution, as prospective data demonstrating benefit from earlier use of KRAS G12C inhibitors are lacking.

P2, N=80, Not yet recruiting, Jiangsu Cancer Institute & Hospital

Moreover, FTY720 co-treatment resensitized G12D NRAS-mutated M14(R)701 cells to gilteritinib in vivo. Co-treatment inactivated ERK, transcriptionally downregulated SPHK1, and inactivated downstream AKT, p70 S6K and BAD, with inactivation abrogated by constitutive SPHK1 expression. The clinically applicable S1PR modulators fingolimod and mocravimod resensitize NRAS-mutated FLT3-ITD AML cells to FLT3 inhibitors, supporting potential clinical efficacy.

Tumor fraction may decrease despite increasing tumor-derived ctDNA during treatment monitoring. Simultaneous evaluation of absolute ctDNA and tumor fraction may improve interpretation of ctDNA dynamics in metastatic colorectal cancer.

We performed multiomic single cell (SC) DNA/protein and RNA/protein profiling of a clinical trial cohort of acute myeloid leukemia (AML) patients treated on the Phase 1b clinical trial of the BCL2 inhibitor venetoclax and the FLT3 inhibitor gilteritinib (Ven/Gilt) to characterize immunophenotypic, transcriptional, and genetic clonal evolution driving resistance. These results underscore that RAS signaling is central to FLT3 and BCL2 inhibitor resistance, is tightly coupled to AML monocytic differentiation and highlight RAS pathway inhibition as a viable clinical strategy to combat resistance. CT# NCT03625505.