KRAS (KRAS proto-oncogene GTPase)

P1, N=58, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Mar 2027 --> Aug 2027

These findings suggest that pregabalin increases the proliferative ability of pancreatic cancer cells in vitro without promoting tumor growth in vivo. Additionally, it induces an alteration with an increase in tumor-infiltrating lymphocytes and dendritic cells, along with a decrease in M2-like tumor-associated macrophages and cancer-associated fibroblasts in vivo.

We critically discuss the apparently conflicting evidence on STK33's essentiality in KRAS-driven cancers, and argue for refined targeting strategies of STK33 (including degradation rather than simply kinase inhibition) alongside biomarker-guided patient stratification. With continued optimization of pharmacokinetics, selectivity, and mechanism of action, STK33 remains a promising, albeit challenging, target in precision oncology.

Colonoscope-derived mucus is a promising localized cfDNA source for detecting early colorectal neoplasia. This approach may serve as a colonoscopy-integrated adjunct within existing screening pathways and may support post-procedure risk stratification and surveillance optimization.

Allele-specific KRAS inhibitors such as the KRASG12C inhibitors sotorasib and adagrasib have demonstrated clinical activity as monotherapy but adaptive signaling in response to KRAS pathway inhibition can promote resistance and limit the efficacy of these drugs. Using xenograft models, we observed that pharmacologic blockade of FAK enhanced the anti-tumor activity of KRAS inhibitors. These data highlight the therapeutic potential of FAK/SRC inhibitors to mitigate adaptive signaling induced by KRAS inhibition and enhance the clinical activity of KRAS inhibitors.

This refinement operates at the cellular level without displacing the tissue-level Correa sequence documented in long-term human cohorts. It nominates the remodelled stem-cell niche as a tractable pharmacological target and warrants molecular profiling of at-risk progenitor populations to complement, rather than replace, histopathological surveillance.

Immunohistochemical analyses of pancreatic cancer tissues revealed high VEGFR2 expression in 83% (67/80) of samples, significantly exceeding the levels observed in normal pancreatic tissues. These results underscore VEGFR2 as a promising molecular target and propose a novel therapeutic avenue for KRAS-mutant cancers.

In this single-arm, phase I study (NCT04117087), we evaluated mKRAS-VAX, a pooled mutant KRAS (mKRAS) peptide vaccine targeting six KRAS mutations with nivolumab and ipilimumab in 13 patients with pretreated metastatic MMRp/MSS CRC. mKRAS-VAX elicited an increase in tumor-specific mKRAS-reactive T-cells in 8/12 biomarker-evaluable patients (75%) by direct ex vivo IFNγ ELISpot and in 12 patients (100%) following in vitro expansion. Our findings support further development of mKRAS vaccines with ICIs for advanced MMRp/MSS CRC.

P2, N=90, Active, not recruiting, Mirati Therapeutics Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2026 --> Sep 2026

These results suggest that high-dose tramadol improves cancer-associated pain but enhances the tumor volume of pancreatic ductal adenocarcinoma by decreasing anti-tumor CD8+ T lymphocytes.

P2, N=150, Not yet recruiting, Verastem, Inc.

This study is the first to examine p27 localization in WT KRAS CRC. The observed association between WT KRAS expression and cytoplasmic p27 localization highlights a potential mechanism contributing to tumour progression through altered p27 function.