KRAS (KRAS proto-oncogene GTPase)

P2, N=13, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=27 --> 13

CCBE1 is an oncogenic driver in colorectal cancer that independently predicts poor survival and functionally enhances tumor cell proliferation, invasion, and M2 macrophage polarization. Targeting CCBE1 may represent a potential therapeutic strategy for colorectal cancer.

Orthotopic KRAS-mutant xenograft models (LOVO-Luc2 (N = 52) and SW480-Luc2 (N = 52)) were treated with standard-of-care regimens (FOLFOX, bevacizumab, or combination) and longitudinally imaged by CT (N = 104 tumour scans, N = 156 liver scans collected over 4 timepoints)...The most predictive features, GLSZM Gray Level Non-Uniformity, GLRLM Run Length Non-Uniformity Normalized, and GLDM Small Dependence Emphasis, were significantly associated with metastatic burden and survival in a clinical CRC cohort (N = 41), indicating species conservation and translational relevance. Collectively, these data demonstrate that preclinical CT radiomics can identify quantitative imaging features associated with treatment sensitivity and early metastatic progression, supporting translational potential.

This systems-level framework provides mechanistic rationale for clinical investigation of intratumoral S. boulardii as adjuvant PDAC therapy. The online version contains supplementary material available at 10.1007/s40203-026-00685-6.

HNF4α also promotes resistance to KRAS inhibition by increasing nuclear factor erythroid 2-related factor 2 (NRF2) activity. These findings may advance therapeutic avenues in IMA.

E/M-CTC ≤ 1 showed a trend toward improved OS (p = 0.086). In addition, patients with > 1 CTC who received local radiotherapy for progressive lesions after glecirasib targeted therapy had significantly prolonged PFS and OS compared to those who did not (p < 0.05).

KRAS mutations are associated with aggressive recurrence patterns and a poor prognosis for patients with CRLM. However, survival following local therapy for recurrence appeared less pronounced regardless of KRAS status.

SBAs display genomic heterogeneity. The novel HGC stratifies these tumors based on homology to foregut or hindgut alterations and may be superior to anatomic location for characterizing pathology. Additional studies are needed to validate and further explore these findings.

Herein we outline the biology and epidemiology of KRAS alterations at the lineage and allele levels, reviewing the clinical evidence for KRASG12C inhibition from the discovery of the recessive switch pocket to sotorasib, adagrasib and other novel molecules, and extending to the non-KRASG12C era, including RAS (ON)- and KRASG12D-selective strategies and early efficacy signals. We propose a 'three-clock, two-window' framework, which includes half-life exposure, occupation retention and extracellular signal-regulated kinase (ERK) rebound calibration of dosing rhythm; a vascular normalization window and an immune/myeloid plasticity window to achieve longitudinal Src homology 2-containing protein tyrosine phosphatase 2/son of sevenless homologue 1 and transverse epidermal growth factor receptor, phosphoinositide 3-kinase-protein kinase-mammalian target of rapamycin synergy. At the same time, we construct and propose a closed loop of exposure, occupation, pathway inhibition, circulating tumour DNA (ctDNA) and imaging by utilizing ctDNA dynamics, phosphorylated ERK rebound and perfusion imaging, as well as myeloid lineage quantification, to improve durable inhibition and overall survival through time-aligned combined effects.

Experimentally, KRASQ61R mutation led to KRAS exon 3 skipping, which in turn could be rescued by expression of U2AF1I24T. Our findings provide evidence that splicing factor mutations can rescue splicing defects caused by oncogenic mutations in a dynamic process of cascading selection.