TMB-H

The signature independently predicted prognosis (AUC: 0.70-0.84) and treatment response: LR patients favored immunotherapy (lower TIDE, higher IPS), while HR patients were sensitive to chemotherapy (e.g., Bosutinib, Tozasertib). This transcriptome-derived m6A-associated prognostic model can effectively predict clinical survival outcomes and therapeutic response in LUAD patients. Combined with immune landscape, genomic mutation profiles and single-cell transcriptomic evidence, this signature provides a reliable basis for personalized risk stratification and rational treatment choice.

P1/2, N=121, Active, not recruiting, Precision Biologics, Inc | Recruiting --> Active, not recruiting | Trial completion date: Jan 2029 --> Nov 2026 | Trial primary completion date: Jan 2028 --> Jun 2026

We demonstrate that TMB is dynamic and rises over time and with select treatment exposures. These findings reinforce how TMB should be interpreted within the broader context and not necessarily viewed as a standalone threshold for initiating immunotherapy in advanced prostate cancer.

We propose that future progress will likely depend on mechanism-based, biomarker-driven approaches that match specific immune evasion patterns with rationally designed interventions, with the goal of extending immunotherapy benefits to broader CRC populations. This narrative review synthesizes peer-reviewed literature from PubMed and clinical trial registries (2015-2025), prioritizing Phase II/III trials and mechanistic studies.

Outcomes appear to be influenced by an interplay of disease context, clonal architecture, and therapeutic strategy rather than individual mutations alone, underscoring the need for integrated molecular profiling and prospective studies to guide management. This study highlights that MS with MR mutations may follow different cellular pathways to evolution.

We present a renal transplant recipient with metastatic small bowel adenocarcinoma harboring a POLE mutation who was treated with pembrolizumab and achieved a complete metabolic response on PET-CT with negative circulating tumor DNA. This case suggests that immune checkpoint inhibitors may be considered in carefully selected transplant recipients with high tumor mutational burden, though risks remain.

We also highlight clinically relevant biomarkers, including MSI/MMR status, tumor mutational burden, immune contexture, Immunoscore, circulating tumor DNA, microbiome profiles, and spatial or AI-assisted multi-marker models. This review summarizes emerging strategies to enhance therapeutic efficacy in CRC and maps each modality to the tumor-intrinsic or tumor-extrinsic resistance barriers it is most likely to overcome.

P1/2, N=55, Recruiting, University of Chicago | Not yet recruiting --> Recruiting

For early-stage POLE-mutated CRC with favorable prognosis, off-label adjuvant immunotherapy may bring unnecessary toxicity risks. It is necessary to conduct rigorous patient selection, comprehensive risk-benefit evaluation, and close monitoring of organ function during treatment, so as to provide reference for the standardized clinical application of ICIs in this population.

In summary, the 6 PANoptosis-related lncRNAs can well predict the prognosis of LUAD patients, which may provide new insight for survival prediction and clinical immunotherapy of LUAD patients.

A single LoF variant in RecQ DNA helicase genes can result in significant DNA repair deficiency, leading to genomic instability and contributing to CRC development in LLS. Therefore, we present evidence for incorporating RECQL5 into genetic testing panels for CRC risk assessment, which would enhance both diagnosis and treatment outcomes.

CT-based radiological features are significantly correlated with TMB status in lung adenocarcinoma. A composite model incorporating these features demonstrates high diagnostic accuracy for identifying high TMB, offering a valuable non-invasive tool for guiding personalized treatment strategies.