MSI-H/dMMR

In EC cells with pre-existing MLH1 promoter methylation, MLH1-KD leads to MSI-H, enhances genomic instability, disrupts Wnt signaling, impairs cellular functions, and inhibits tumor growth, highlighting Wnt signaling and MSI-H as potential therapeutic targets in EC.

P2, N=12, Not yet recruiting, Meng Qiu

P1, N=160, Recruiting, SystImmune Inc. | N=120 --> 160

P2, N=0, Withdrawn, Assistance Publique - Hôpitaux de Paris | N=43 --> 0 | Not yet recruiting --> Withdrawn

Given the advanced dMMR status of the primary lesion, neoadjuvant immunotherapy with pembrolizumab was administered, resulting in marked radiologic tumor regression...This case represents a rare intra-patient demonstration of dMMR status, together with a CD8-rich tumor microenvironment, conferring considerable sensitivity to ICI therapy, and pMMR status exhibiting resistance, despite identical systemic immune exposure. Our findings suggest that MMR status may serve as a clinically relevant biomarker for response to neoadjuvant immunotherapy in CRC and highlight the importance of independent biomarker assessment for each synchronous tumor.

In metastatic CRC patients who receive nivolumab-based combination therapies demonstrate partial tumor responses that increase while their safety profile remains acceptable, but their overall response rates do not improve. The research demonstrates how immunotherapy serves as a standard treatment method for MSI-H disease while emphasizing the need to develop biomarker-driven approaches that enhance treatment selection methods, especially for MSS CRC.

In addition, we develop and validate a classification model that distinguishes LS carriers from controls using circulating TCRβs signatures associated with LS independent of thecancer history and with cancer-free LS previvors. Together, our findings characterize circulating and tissue TCRβs associated with LS, thus representing a step toward identifying blood-based TCR biomarkers for immune surveillance.

As oncology evolves toward molecular precision, living tumor-agnostic guidelines are critical for ensuring equitable, evidence-informed care for all patients, particularly those with rare cancers. National organizations must prioritize their development to fully realize the promise of precision medicine.

Low BLM RNA expression is associated with improved survival after treatment with DNA-damaging agents, whereas low RAD51 expression shows a favorable but nonsignificant trend. These findings are exploratory and suggest that RNA-based HR gene expression may warrant further investigation as a potential prognostic biomarker in metastatic CRC.

PRKD3 expression also correlated with immune checkpoint molecules including PD-1, PD-L1, and CTLA-4, supporting an immunosuppressive role, while context-dependent associations with TMB and MSI highlighted its potential influence on tumor immunogenicity and responsiveness to immune checkpoint blockade. Collectively, these findings identify PRKD3 as a potential context-dependent modulator of tumor biology, prognosis, and immune interactions, underscoring its potential as a biomarker of diagnostic, prognostic, and therapeutic relevance in precision oncology.

Treatment with D1 LND is recommended for gastric neuroendocrine carcinoma (g-NEC), g-NET with lymphadenopathy, and grade 3 disease. Lymphadenectomy generally is unnecessary for g-GIST, except for those with persistent lymphadenopathy after neoadjuvant therapy or uncommon mutations.

P1/2, N=48, Active, not recruiting, Servier Bio-Innovation LLC | Trial completion date: Aug 2026 --> Aug 2027 | Trial primary completion date: Aug 2026 --> Aug 2027