KRAS mutation

P2, N=50, Enrolling by invitation, Second Affiliated Hospital, School of Medicine, Zhejiang University | Not yet recruiting --> Enrolling by invitation | Trial completion date: Nov 2027 --> Dec 2028 | Trial primary completion date: Nov 2027 --> May 2027

Sufficient exposure to RMC-4630 and LY3214996 was not reached due to the toxicity profile of the combination. Tumor response was not demonstrated at the explored dose levels. Therefore, the dose escalation was discontinued, and the RP2D was not determined.

Both KRAS "OFF"" G12C inhibitors, sotorasib and adagrasib, are considered standard second-line therapy, albeit with a modest progression-free survival benefit over standard chemotherapy. Critical clinical questions remain open regarding the optimal patient population for combinations, the influence of co-occurring genomic alterations, intracranial activity of KRAS inhibitors and dose optimization. This review synthesizes current evidence on the biology, clinical efficacy, safety, and practical considerations for treating KRAS G12C-mutant NSCLC, providing clinicians with an up-to-date, evidence-based framework for therapeutic decision-making and highlighting areas requiring further investigation.

In vivo xenograft models confirmed that the combination of RO and ADA significantly reduced tumor growth. These findings suggest that RO and ADA act synergistically against KRAS-mutant tumors by suppressing NRF2, supporting their potential as a targeted combination strategy for KRAS-driven cancers.

This study clarifies the association between TRGs expression and the biological characteristics of LUAD, highlighting their potential clinical significance in molecular typing and therapeutic guidance, and laying a foundation for personalized diagnosis and treatment strategies for LUAD.

Overall, she had an unusual pattern of disease progression in molecularly low-risk CRC, indicating that delayed CNS metastasis can occur despite apparent systemic remission. These findings challenge current assumptions regarding CNS risk stratification in CRC and raise important questions about the need for individualized neurological surveillance strategies in selected patient subgroups.

Abcb1a/1b-mediated transport of daraxonrasib across the BBB was validated by oral co-administration of the ABCB1/ABCG2 inhibitor elacridar, resulting in 20-fold increased brain penetration in wild-type mice (P < 0.01). ABCB1 function could limit brain penetration and possibly efficacy of daraxonrasib against brain metastases. Collectively, these preclinical findings may help in optimizing the application of daraxonrasib in clinical settings.

P1, N=364, Recruiting, Astellas Pharma Inc

P2, N=300, Not yet recruiting, Federation Francophone de Cancerologie Digestive

Our study identified key gene-based genotypes (Type II/III) of distinct GEPNEC patients and yielded their prognosis and therapeutic utility.

PDC treatment significantly suppresses tumor growth in in vivo KRAS mutant xenograft model, demonstrating superior efficacy compared with cetuximab-based regimens and controls, without observable body weight loss. This strategy uses EGFR as a delivery portal instead of a signaling target, enabling KRAS independent anti-tumor activity. These findings indicate a non-canonical EGFR mediated delivery approach with potential translational relevance for the treatment of therapy resistant CRC.

In this issue of Cancer Cell, Entrialgo-Cadierno et al. raise the bar for the ∼20%-25% of patients with oncogenic KRAS mutations by unlocking the therapeutic potential of direct RAS-GTP inhibition.