RAS wild-type

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.

NF1 mutation is the strongest gene-level correlate of lung-selective metastasis in cutaneous melanoma. The NF1-mutant subtype may represent a dual-biomarker population and could warrant both pulmonary surveillance and prospective evaluation for immunotherapy.

P2/3, N=574, Recruiting, SUNHO（China）BioPharmaceutical CO., Ltd. | N=90 --> 574 | Trial completion date: Jul 2028 --> Jul 2029 | Trial primary completion date: Jul 2026 --> Jul 2028

P3, N=400, Recruiting, Seagen, a wholly owned subsidiary of Pfizer | Trial completion date: Jul 2029 --> Jul 2030 | Trial primary completion date: Apr 2026 --> Dec 2027

P1/2, N=155, Recruiting, Lyell Immunopharma, Inc. | Phase classification: P1 --> P1/2 | N=30 --> 155

P2, N=60, Recruiting, Vall d'Hebron Institute of Oncology | Trial completion date: Dec 2025 --> Jul 2032 | Trial primary completion date: Sep 2025 --> Jul 2032

Poor survival outcomes were observed across all 1 L treatment options. Patients with KRAS-mutated NSCLC and low PD-L1 expression had especially poor outcomes, highlighting the need for more effective treatment options.

This review summarizes current evidence on the crosstalk between KRAS signaling and Furin-like enzymes, emphasizing their cooperative roles in tumour progression and immune escape. Targeting protein maturation by these enzymes may therefore represent a therapeutic approach for KRAS-mutant colorectal cancer, offering new opportunities for personalized treatment.

P2, N=216, Completed, Melanoma Institute Australia | Trial completion date: Dec 2025 --> Mar 2026

High Cdc42 expression may serve as an adverse prognostic marker in CRC. Cdc42 shows moderate concordance between primary tumors and matched metastases without a consistent directional shift.

HER2 positivity is associated with reduced response to anti-EGFR therapy and independently predicts shorter PFS in patients with RAS wild-type mCRC. These findings further support the role of HER2 as a clinically relevant biomarker in RAS wild-type mCRC, particularly in predicting response to anti-EGFR therapy, while highlighting the need for optimized patient selection strategies in the era of HER2-targeted treatments.

This study showed that the status of APC mutation may be associated with clinical outcomes in patients receiving cetuximab-containing chemotherapy in RAS wild metastatic CRC. Further prospective studies are warranted to validate and incorporate APC mutation into clinical decision-making algorithms.