KRAS amplification

This exploratory analysis suggests pERK expression and mutation of KRAS/BRAF/NRAS are candidate biomarkers of improved PFS and response to trametinib, respectively.

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.

Furthermore, combining TNK2/ACK1 inhibitors with anti-PD-1 immunotherapy or with nab-paclitaxel plus gemcitabine demonstrates promising antitumor efficacy in both allograft and spontaneous PDAC models. Overall, our findings reveal a mechanism of immune evasion and provide a potential framework for developing tailored immunotherapeutic strategies in PDAC.

Both cases were managed with capecitabine-oxaliplatin plus bevacizumab, followed by maintenance therapy, achieving disease stabilization for at least 9 months. Given the rarity of STM, especially in metastatic or recurrent settings, there is an urgent need for standardized diagnostic protocols and evidence-based treatment strategies. These cases support the use of tumor-specific chemotherapy regimens guided by the histological and molecular characteristics of STM.

P1, N=45, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial primary completion date: Aug 2025 --> Jul 2026

Plasma cfDNA analysis using NGS is feasible and offers insights into alectinib resistance mechanisms. Early detection of resistance-associated mutations may guide personalized treatment strategies. Larger prospective studies are needed to validate these findings.

P1, N=47, Active, not recruiting, Boehringer Ingelheim | Trial completion date: May 2027 --> Dec 2025 | Trial primary completion date: May 2027 --> Dec 2025

RAS, PIK3CA, and HER2 mutations can commonly co-occur with HER2 amplification, with higher rates in colon cancer than rectal cancer. These findings underscore biological heterogeneity and the importance of molecular profiling in identifying potential resistance before initiation of HER2-directed therapy.

P1, N=47, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting | N=146 --> 47

P3, N=589, Active, not recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Recruiting --> Active, not recruiting

This multiplex dPCR method detected all target mutations with a limit of detection below 0.2% while quantifying CNAs. Additionally, the assay accurately quantified variant allele frequencies in liquid biopsy and tissue samples from both pancreatic neoplasm precursor and PDAC patients, indicating its potential for use in comprehensive patient follow-up.

Both FGF PV and KRAS are the independent factors for poor prognosis. To our knowledge, this is the first report to describe an inflamed microenvironment recruited by NOTCH1/RB1 co-mutation, indicating potential benefit from immunotherapy.