TMB-H

The results of this real-world study demonstrate that endometrial cancer is a complex disease, characterized by substantial molecular heterogeneity and varying biomarker distributions across histology, stages, and molecular subtypes. This real-world study supports the integration of comprehensive molecular profiling into routine practice to refine prognostic stratification and guide biomarker-driven therapies.

Initially diagnosed with BRAF V600E-mutated melanoma, he received Dabrafenib and Trametinib...Despite initial treatment with Triptorelin, Docetaxel, and Abiraterone, disease progression occurred...This case illustrates the value of precision medicine and the role of liquid biopsy in guiding immunotherapy decisions for complex oncological cases. It supports the relevance of molecular profiling in selecting effective treatments beyond standard indications.

Survival differences were independent of WHO diagnostic labels, with molecular architecture alone consistently predicting outcomes across all clusters In this Indian MPN cohort, molecular architecture, not WHO label, dictated prognosis. The reproducible impact of high-risk co-mutations demonstrates both the feasibility and need for a genomics-first, tiered classification to guide risk stratification and therapy.

It discusses the major trials of nivolumab, pembrolizumab, and ipilimumab, including combinations from the CheckMate-142 and CheckMate-8HW trials. The combination of PD-1 and CTLA-4 inhibitors in MSI-H/dMMR metastatic colorectal cancer has demonstrated long-term clinical efficacy and a genuine survival benefit. However, in MSS metastatic colorectal cancer, there has been limited response, emphasizing the importance of innovative combination therapies to address both primary and secondary resistance.

Mutation burden is a key determinant of IST response, while TP53 and DNMT3A mutations signal poorer long-term outcomes. Mutational profiling may improve risk stratification and guide personalized management.

TMB-high status (≥10 mut/Mb) showed a numerically higher, but not statistically significant, rate of pathological complete response among patients receiving neoadjuvant ICI and significantly associated with more favorable time to recurrence in patients receiving adjuvant ICI, particularly among patients with PD-L1 expression <50%. TMB should be considered in future early-stage NSCLC ICI clinical trials to further validate these results.

However, there may be benefits in selected tumors harboring mutations with microsatellite instability high/mismatch repair deficiency (MSI-H/dMMR) and, to a lesser extent, high tumor mutational burden (TMB-H). While only a small percentage of prostate tumors have these mutations (MSI-H/dMMR: 3%) and (TMB-H: 4.5%), panel genomic testing can help identify subsets of patient populations who may benefit from PD-(L)1 inhibitors in addition to other molecularly selected agents.

This case highlights the power of comprehensive molecular profiling and high-frequency ctDNA monitoring to capture tumor evolution and minimal residual disease. Importantly, it further demonstrates how MRD-guided surveillance enables a precise balance between fast-acting targeted therapy and the sustained effects of immunotherapy, providing a blueprint for individualized, context- driven treatment strategies in rare molecular subtypes of pancreatic cancer.

Molecular profiling revealed a high prevalence of actionable biomarkers in CUP and was associated with improved survival with guided therapy. These findings support the integration of molecular profiling into routine clinical practice for CUP management to enable precision oncology and improve patient outcomes. Further prospective validation is warranted.

This review explores the current landscape of both established and emerging biomarkers that influence immunotherapy sensitivity and their implications for surgical intervention as a treatment strategy. Established biomarkers such as programmed death-ligand 1, microsatellite instability, and high tumor mutational burden are used to predict responses to immune checkpoint inhibitors and inform perioperative strategies.

Elucidating these pathways will be critical for optimizing treatment strategies and improving clinical outcomes in malignancies such as NSCLC. This review highlights the critical role of these pathways in optimizing treatment strategies and improving clinical outcomes in malignancies such as NSCLC.

Multiple-classifier ECs represent a small but clinically relevant subset encompassing biologically heterogeneous entities. Our findings highlight the limitations of current molecular classification hierarchies and underscore the need for harmonized molecular testing and standardized reporting to improve risk stratification and the management of multiple-classifier ECs.