RAS wild-type

Stratified two-stage TMP reliably identifies actionable alterations in PC patients, with potential therapeutic benefit. The proposed TMP algorithm might be as effective, yet more feasible and economic compared with comprehensive upfront testing.

Notably, actionable gene fusions were found to be significantly enriched in KRAS-wt EO-PDACs compared with LO counterparts (4 versus 1, or 36.4% versus 2.4%, P = 0.005). KRAS-wt PDAC diagnosed at a younger age more frequently harbors actionable mutations, highlighting the importance of comprehensive genomic profiling to guide targeted therapeutic interventions in this patient population.

Multiplex immunofluorescence staining demonstrated that BCL-xL inhibition effectively triggered apoptosis in heterogeneous PDX tumor slice models, including models harboring oncogenic BRAF mutations. Our findings suggest that cetuximab-resistant CRC retains apoptotic competence, and that BCL-xL inhibition serves as a robust alternative therapeutic strategy that is largely independent of the tumor mutational profile.

P2, N=477, Suspended, Gruppo Oncologico del Nord-Ovest | Trial completion date: Dec 2027 --> Dec 2029 | Recruiting --> Suspended | Trial primary completion date: Oct 2025 --> Oct 2027

P2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

KRAS mutant non-sq LA-NSCLC is associated with inferior outcomes, largely driven by increased distant and brain metastases. Tumors with concurrent CDKN2A and/or STK11 alterations had the poorest outcomes. These findings support the evaluation of KRAS inhibitors in this high-risk stage III population.

P2, N=90, Not yet recruiting, The First Affiliated Hospital of Henan University of Chinese Medicine; The First Affiliated Hospital of Henan University of Chinese Medicine

P1/2, N=178, Not yet recruiting, Shanghai Eastern Hospital; Nerviano Medical Science Shanghai Ltd.

P1/2, N=120, Recruiting, Shanghai East Hospital; Novatim Immune Therapeutics (Zhejiang) Co., Ltd.

Conversely, KRAS-wild-type cells preserve NAD+ influx via sufficient baseline succinyl-SLC25A51, which stabilizes SLC25A51 and enables sufficient succinate accumulation to drive hypoxia inducible factor 1 subunit alpha (HIF1α)-mediated compensatory NAD+ production during treatment. Our work reveals a KRAS-specific metabolic vulnerability and proposes a dual-inhibition therapy for KRAS-driven AML.

P1, N=194, Recruiting, Hefei TG ImmunoPharma Co., Ltd.

Within surgically treated patients, baseline CA19-9 emerged as the most informative prognostic marker, while traditional clinicopathologic variables showed limited discriminatory value. These findings highlight the importance of careful patient selection and support further prospective studies integrating molecular and biomarker-based strategies to refine prognostication and optimize surgical decision-making in RAS-WT mCRC.