KRAS mutation

P1/2, N=370, Recruiting, Revolution Medicines, Inc.

This article examines the clinical and translational application of specific next-generation blood-brain barrier penetrant KRASG12C inhibitors, such as sotorasib, adagrasib, olomorasib, RMC-6236, and D3S-001, and their rational integration with radiation therapy, targeted therapies, and immunotherapies to overcome therapeutic resistance in patients with NSCLC brain metastases. This review summarizes recent advances aimed at enhancing intracranial tumor control and overall survival in patients with NSCLC brain metastases through the use of next-generation KRASG12C inhibitors and multimodal therapies.

P=N/A, N=13, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Further, the addition of KO-2806 rescued sensitivity of progressing tumors to the pan-RAS inhibitor RMC-6236. These results establish mTORC1 as an important mediator of escape from RAS inhibition and highlight KO-2806 as a promising RAS companion inhibitor in patients with prior RAS inhibitor exposure.

Increased OS with immunotherapy was noted only in patients who did not have surgery, radiation, or chemotherapy. These results seem somewhat disappointing given the enthusiasm for immunotherapy.

Spectral CT offers a non-invasive method to assess genetic mutations and prognostic factors associated with colorectal primaries. The lack of standardization in technology and measurement methods limits its applicability in clinical practice.

For patients receiving cytarabine-based front-line chemotherapy, those with RAS mutations had shorter median OS compared to RAS-wild-type AML (27.1 vs. 122.2 months, p < 0.001)...Although 80 (66.1%) of 121 total RAS mutations were found in codons G12 or G13, most substitutions were G12D or G13D, which are not targetable by commercial RASG12C inhibitors. This study sheds light on prognostic implications of RAS mutations and may inform extension of the therapeutic reach of RAS inhibitors to AML.

Among different gene alteration subgroups for advanced NSCLC, the efficacy of first-line ICIs did not differ with statistical significance, with high PD-L1 expression as a predictive factor for better survival. In KRAS mutant patients, KRAS G12C mutation or TP53 co-mutation might indicate improved survival.

Compared to other models, Local-Global Mutation Network (LG-MutaNet) consistently outperformed traditional ML and DL algorithms. The LG-MutaNet, combining CT imaging and clinical variables, offers a non-invasive and precise approach for predicting EGFR and KRAS mutations in NSCLC patients, supporting personalized treatment decisions and advancing precision medicine.

This study underscores the diverse genetic mutations occurring in NSCLC patients with varying risk factors. The identification of TP53 co-mutations provides critical insights for personalized immunotherapeutic strategies and optimizing treatment outcomes.

EBUS-TBNA's role in diagnosing various conditions, especially primary lung cancer, is clear. Clinically, EBUS-TBNA provides genetic diagnoses, which can enable immunotherapy. Patient satisfaction is high, with patients expressing relief after the procedure and finding the staff exceptional.

In conclusions, SOX8 functions as a molecular hub linking KRAS and TGF-β pathways, promoting epithelial-mesenchymal transition (EMT), invasive capacity, and chemotherapy resistance. This novel KRAS-SOX8-TGF-β axis plays the important role in invasion and metastasis of pancreatic cancer, suggesting SOX8 as a useful prognostic biomarker and therapeutic target.