MSI-H/dMMR

P1, N=30, Recruiting, Radiopharm Theranostics, Ltd | N=23 --> 30 | Trial completion date: Oct 2025 --> Dec 2027 | Trial primary completion date: Jul 2025 --> Dec 2027

P1, N=464, Not yet recruiting, Amgen

P2, N=114, Not yet recruiting, Fudan University

The frequency of TMB-high was 4.4%, which is slightly higher than that previously reported. Pembrolizumab demonstrated greater efficacy in patients with MSI-H plus TMB-high while also exhibiting some efficacy in patients with MSS plus TMB-high.

Molecular sub-types in endometrial cancer reflect distinct and reproducible phenotypes. However, classic histopathologic features remain the strongest predictors of nodal spread and SLN detection failure.

P3, N=164, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Feb 2027

The frequency of MSI cases in this study is congruent with global trends, highlighting the importance of microsatellite status in GC for understanding clinicopathological differences between MSI and MSS patients. These findings support the potential of MSI status as a biomarker.

Cross-cohort analysis further revealed that despite favorable immunological features (higher TMB, neoantigen load, memory-activated CD4+ T cells, activated NK cells, mast cells, M1 macrophages and immune checkpoint expression), MSI-H gastric cancers have heterogeneous immunotherapy outcomes. Collectively, dMMR/MSI-H status alone is insufficient for outcome prediction, highlighting the need for individualized TIME evaluation in patients with gastric cancer receiving immunotherapy.

In this study, we characterized resistance mechanisms using the clinical candidate HRO761 and two novel inhibitors in MSI cell lines and xenograft models...This chemotype-specific resistance profile suggests opportunities for developing next-generation inhibitors that retain activity against resistant variants and for implementing rational treatment strategies with existing inhibitors. Overall, our findings demonstrate that on-target resistance to WRN inhibitors emerges rapidly in dMMR backgrounds but also highlight potential approaches to overcome resistance, supporting continued development of WRN-targeted therapies for MSI cancers.

RWE confirms the effectiveness and safety of multiple recently approved oncology drugs reinforcing the external validity of RCTs.

This study provides a regional molecular profile of advanced CRC in Bulgaria, highlighting a high prevalence of KRAS mutations and dMMR status, while underrepresentation of rare targetable alterations, likely due to limited use of broad molecular profiling. The association between stromal features and MMR status supports their potential role as surrogate markers in settings with constrained testing resources. Findings underscore the urgent need for equitable access to molecular diagnostics and targeted therapies to close the survival gap between Eastern and Western Europe.

We also discussed implementation challenges, including test standardization, reporting, equity of access, and areas of ongoing uncertainty. This position paper aims to support consistent, equitable, and biologically informed management of endometrial carcinoma in contemporary practice.