KRAS mutation

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.

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.

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.

Patients in the high-risk group exhibited characteristics associated with worse outcomes, including KRAS mutations, chemoresistance, an immunosuppressive microenvironment and reduced responsiveness to immunotherapy. The present study establishes HRH1 as a novel therapeutic target in PDAC and proposes the repurposing of fexofenadine as a promising strategy to disrupt the oncogenic HRH1-YAP1 feedback loop.

Analytical power analysis revealed that for most treatments and/or cancer types, the cohort sizes remain underpowered. Systematic identification of nonresponse signals reveals multiple potential biomarkers that will require larger cohort sizes for prospective clinical implementation.

This may explain why PARP7i were more effective as monotherapy in PANC-1 cells, promoting NK cell activation. These findings support further evaluation of PARP7i in PDAC in combination with radiotherapy or as monotherapy, depending on the immunosuppressive effects of radiation.

P1/2, N=222, Not yet recruiting, Genfleet Therapeutics (Shanghai) Inc.

P2, N=19, Active, not recruiting, Georgetown University | Recruiting --> Active, not recruiting | N=54 --> 19

The frameshift mutation of ETV6:c.744del may serve as a potential driving factor. It is recommended that germline genetic testing and family screening be conducted for all pediatric patients with familial clustering of leukemia.