KRAS wild-type

In addition, 089 exhibited good tolerability in a nude mouse HCT-116 xenograft model, but it was less effective at a dose of 40 mg/kg compared with Apremilast at a dose of 30 mg/kg in 8-s day's assay. While 089 had lower in-vivo efficacy than apremilast, its novel 3-aminoisoquinoline scaffold and high tolerability make it a superior candidate for further optimization.

In first-line ICI-treated stage IV NSCLC, KRAS-KEAP1 co-mutation, not KRAS or KEAP1 alone, identifies patients at high risk of early failure, whereas BRAF was associated with longer TTF. These findings highlight the importance of co-mutation profiling and warrant prospective validation with integrative models incorporating PD-L1 and TMB.

This study is the largest longitudinal analysis of KRASM testing conducted in Australia, with significant improvement in testing rates seen over the time period. Rates of KRASM and characteristics of Australian KRAS mt patients correspond with published literature.

Incorporating a structured diagnostic algorithm that recognizes rare subtypes and integrating comprehensive genomic profiling into routine practice represents a paradigm shift from non-stratified to mechanism-driven therapy in pancreatic cancer. This narrative review summarizes the clinicopathological characteristics, molecular landscapes, and therapeutic opportunities of rare PDAC subtypes, highlighting how precision medicine can reshape prognosis and treatment in a historically hard-to-treat disease.

Emerging immunotherapies targeting Claudin18.2 and CXCR4 offer hope to overcome tumor resistance. Together, these strategies underscore the promise of molecular stratification, synthetic lethality, and novel targets to improve pancreatic cancer survival.

Results of subcutaneous tumor and pulmonary metastasis models exhibited a similar conclusion to in vitro experiments. Butyrate reduces cetuximab efficacy in KRAS wild-type colorectal cancer through EGFR and AMPK-Wip1 signaling, and may represent a candidate predictive biomarker for treatment response.

Furthermore, compared with 3' end nucleotide derivative modifications, 5' end capping is more effective at increasing ribozyme stability and compatibility with in vitro preparations. These features underscore the promising potential of natural pistol ribozymes as advanced therapeutic nucleic acid molecules for targeting KRAS mutation-driven cancers and suggest a generalizable strategy for structure-guided, allele-specific RNA therapeutics.

P1, N=132, Recruiting, Conjupro Biotherapeutics, Inc. | Trial completion date: Dec 2025 --> Aug 2027 | Trial primary completion date: Jun 2025 --> May 2027

Consistently, a risk-score based on the NETosis-MAPK signaling interaction is significantly associated with poorer survival in human PDACs. This study thus provides a new venue for overcoming resistance to strategies targeting KRAS signaling.

Recurrence risk among patients with R0N0 pCCA was heterogeneous. The proposed risk score stratified patients into markedly different risk categories relative to recurrence, which may help guide utilization of adjuvant therapy as well as surveillance in the postoperative setting.

P1/2, N=282, Recruiting, Shionogi | Trial completion date: Apr 2027 --> May 2028 | Trial primary completion date: Apr 2027 --> May 2028

E2A is overexpressed in lung adenocarcinoma and is significantly elevated in tumors harboring mutant KRAS. These findings identify E2A as a context-specific suppressor of TGF-β-mediated apoptosis and a potential therapeutic target in mutant KRAS NSCLC.