KRAS wild-type

Integrated clinical, genomic, and histopathological analyses revealed a high frequency of lymph node-negative, intraductal papillary mucinous neoplasm (IPMN)-associated cancers, KRAS and/or SMAD4 wild-type tumors, and classical subtype by immunohistochemistry, all collectively associated with more favorable outcomes. Acknowledging the highly selected nature of this cohort, isolated intrapancreatic metastases demonstrate a more indolent biology and these patients may benefit from personalized management approaches beyond traditional paradigms.

Persons who have a more pro-inflammatory lifestyle may have an increased recurrence risk (IRR 1.21, 95% CI 0.97-1.52), which was most pronounced for persons with MSS and KRAS or PIK3CA wildtype tumours (IRR 1.31, 95% CI 0.90-1.90 and IRR 1.30, 95% CI 0.98-1.71, respectively). Our results suggest that associations between the LIS and recurrence might differ based on molecular tumour characteristics.

This meta-analysis shows that KRAS, NRAS, and BRAF mutations are important for adverse prognostic markers in colorectal cancer, linked to reduced overall survival. Routine molecular testing for these mutations is vital to enable personalized treatment, improve patient stratification, and enhance clinical outcomes in colorectal cancer management.

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.

Three KRAS-mutated tumors also had at least focal mesonephric-like histology. Although rare, p53 wild-type tumors represent a small subset of OCS that show distinct clinical and histologic features and are largely driven by KRAS mutations.

P1, N=434, Recruiting, Amgen | Trial completion date: Oct 2030 --> Apr 2031 | Trial primary completion date: Oct 2027 --> Apr 2028

AKR1B10 facilitated immune evasion of KRASG12C mutation CRLM by recruiting and reprogramming neutrophils to remodel the immunosuppressive TME, providing a potential therapeutic target for KRASG12C mutation CRLM patients.

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.

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

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