KRAS G12D

Histopathological evaluation may aid risk stratification alongside KRAS status. Prognostic assessment in clinical settings should take both TNM staging and KRAS status into account.

Furthermore, we validated the specificity of our approach by successfully detecting various mutations, including KRAS G12C, KRAS G12D, EGFR T790M and TP53 R273H, in simulated clinical samples. These findings highlight a reliable method for precise ctDNA detection, offering high specificity, selectivity, and accuracy, thus paving the way for potential cancer diagnostic application.

Mutational analysis further highlighted the significance of KRAS G12C, G12V, and G12D mutations, which were common between RCC and pancreatic metastasis. Our study provides critical insights into the statistically significant associations between metabolic disorders and malignancies, emphasizing the potential of tailored therapies alongside shared therapies in managing RCC and its progression to pancreatic metastasis.

There is a need to understand how the LUAD TME impacts patient response to immunotherapy. We identified a transcriptional program enacted by TAp73 in tumor alveolar macrophages that supports T-cell activation. Transcriptional and metabolomic data from LUAD patients supports the relevance of this program in response to immune checkpoint inhibition.

The landmark approval of Sotorasib in 2021, the first covalent KRASG12C inhibitor, shattered this dogma, ushering in a new era of targeted therapy for KRAS-mutant cancers, which also has catalyzed an explosion of innovative strategies extending far beyond covalent G12C targeting...Additionally, it encompasses structure-activity relationship (SAR) investigations and activity optimization processes and pharmacokinetic properties studies of representative molecules. Furthermore, we critically evaluate existing challenges in developing small-molecule KRAS modulators while discussing emerging opportunities in overcoming on-target resistance, aiming to offer valuable insights and perspectives for future research in this rapidly evolving field.

PBAE-PEG/LNP delivery of sgRNAs targeting Eml4 (sgEml4) and Alk (sgAlk) into Cas9 mice by IT injection produced autochthonous lung tumors carrying the driver oncogene Eml4-Alk. This approach using PBAE-PEG/LNP to deliver RNA will allow for agile development of lung cancer mouse models.

Our data further demonstrated that pharmacological or genetic inhibition of c-Myc effectively reversed the resistance phenotype mediated by HDAC5 loss, suggesting a therapeutic strategy centered on "KRAS-MYC dual-node blockade." Furthermore, the expression levels of HDAC5 and the acetylation status of c-Myc may serve as potential biomarkers for predicting the therapeutic response to MRTX1133. These findings provide insights into overcoming resistance to KRASG12D inhibitors and offer potential biomarkers and combinatorial therapeutic strategies for precision treatment of PDAC.

These findings reveal that Sod2 shapes cellular metabolism in pancreatic cancer through peroxynitrite formation and Myc activation.

We described the genomic landscape of KRASG12D-mutant CRC and PDAC, demonstrating that cases often have additional oncogenic alterations linked to resistance to KRAS inhibition. These alterations are also associated with a worse prognosis. Recognizing these alterations may inform new therapeutic strategies. Further studies are warranted to validate these findings in ongoing clinical trials.

EMP1 plays a crucial role in the pathogenesis of PDAC, as it contributes to the proliferative and metastatic characteristics of PDAC. This study suggests that EMP1 may be a potential therapeutic target gene for aggressive disease.

Overall, we report that Sitagliptin and Linagliptin have significant anticancer potential towards KRAS-mutated PDAC. Furthermore, we recommend repurposing of more drugs to examine their anti-cancer potential towards these aggressive cancers and to overcome clinical resistance in the near future.

By adding nimotuzumab to existing gemcitabine-based AC regimens, RPC patients would show a survival benefit trend with a satisfactory safety profile.