MSI-H/dMMR

P2, N=128, Enrolling by invitation, Blokhin's Russian Cancer Research Center

P3, N=190, Recruiting, Taizhou Hanzhong biomedical co. LTD | Not yet recruiting --> Recruiting | Trial primary completion date: Jan 2026 --> Jun 2026

In conclusion, for endometrial cancer patients exhibiting dMMR by IHC but MSS by MSI testing, MLH1 promoter methylation testing becomes even more critical. This not only aids in screening for Lynch syndrome, enabling pathologists to make a more precise diagnosis, but also provides important guidance for clinical treatment decisions.

Cadonilimab combined with chemotherapy demonstrated clinically meaningful activity and manageable safety as first-line treatment for advanced or recurrent EC, supporting further investigation, particularly in molecularly defined populations.

Mixtures of DNA prepared as a model of variable tumor content further demonstrated expected attenuation of MSI-associated signals with decreasing tumor fraction, while remaining detectable at multiple loci under low-tumor-content (10%) conditions. Together, these results demonstrate that MSIanalyzer detects read-level microsatellite diversity and enables quantitative, distribution-level characterization of MSI patterns, providing a foundation for mechanistic studies of repeat instability and future clinical validation.

Collectively, these findings demonstrate that USP13 stabilizes SOCS1 by removing K63-linked ubiquitination, thereby restraining excessive JAK-STAT activation and reversing resistance to αPD-1 therapy in MSI-H CRC. Targeting the USP13-SOCS1 axis may therefore represent a promising combination immunotherapeutic strategy for MSI-H CRC.

In this real-world PSM study, MSI-H/dMMR CCA was associated with markedly improved survival and durable clinical benefit from ICI-based therapy, with a manageable safety profile. These findings support MSI-H/dMMR as a key actionable biomarker and underscore the importance of routine MSI testing in CCA.

Integrated exome/transcriptome profiling with MSI quantification identified MSI burden and adaptive immune repertoire diversity as potential correlates of response and survival following ICB. These findings suggest a mechanistic link between genomic instability, antigen recognition diversity, and immunotherapy benefit.

Results from the DRUP trial suggest that off-label targeted cancer therapies produce meaningful benefit primarily in tumors with well-validated biomarkers, such as MSI-H, echoing findings from prior basket studies. The study also demonstrates how systematically collected real-world outcomes data can inform reimbursement decisions and help determine which tumor-agnostic strategies are both clinically useful and economically justified.

More recently, the efficacy of ICIs has also been demonstrated in localized disease, prompting new questions regarding their integration into curative-intent strategies, such as the risk of overtreatment given the favourable prognosis of early-stage tumours, the role of nonoperative management, the optimal treatment regimen, and schedule. In this review, we summarize the available literature and the evidence supporting treatment strategies for patients with early- and advanced-stage MSI-H/dMMR non-colorectal cancers.

After surgery, there was no pathological evidence of residual adenocarcinoma. This case demonstrates the potential of pembrolizumab in paediatric CRC, highlighting the importance of molecular-guided rather than age-restricted therapy selection.