TEST:

MSK-IMPACT

NRAS-mutant melanomas harbor a coordinated transcriptional program within 1p13.2, driven by CNV gains. This locus contains genes with potential druggability, offering new avenues for combinatorial targeting alongside mitogen-activated protein kinase pathway inhibition.

P1, N=14, Not yet recruiting, PMV Pharmaceuticals, Inc

P1/2, N=52, Recruiting, Memorial Sloan Kettering Cancer Center

Kaplan-Meier analysis of R-CHOP-treated patients with DLBCL-NOS revealed that those with MCD, BN2, and A53 subtypes had poorer overall survival than those with EZB and ST2, particularly among patients with concurrent MYC/BCL2 DE. Using a clinically applicable NGS panel, we successfully implemented the LymphGen classification system. This study underscores the distinct genetic landscape of Korean DLBCL and highlights the utility of LymphGen in identifying high-risk subgroups, providing a basis for prognostic stratification and therapeutic optimization.

RRASQ87L and RRAS2Q72L are recurrent, oncogenic, and potentially actionable drivers in NSCLC. Our study supports the inclusion of RRAS/RRAS2 into routine molecular diagnostic panels for precision oncology and provides preclinical rationale for investigating the potential therapeutic utility of pan-RAS inhibitors for patients with RRASQ87L/RRAS2Q72L-mutant lung cancers.

The DDR-IF score unifies measures of genomic instability and immune contexture to identify a therapeutically vulnerable subset of ES-SCLC patients most likely to benefit from PARP-ICB synergy. It represents a promising, though exploratory, framework for personalizing immunotherapy in ES-SCLC, whose clinical utility requires confirmation in prospective multicenter trials.

Notably, 7 individuals (22%) experienced severe or fatal therapy-related toxicities, despite many lacking other clinical features of a TBD. These findings support that RTEL1 R1264H can act in an autosomal dominant fashion and confer TBD disease risk, albeit with low penetrance, and may increase susceptibility to treatment-related complications.

PRNRP represents a distinct KRAS-mutant RCC subtype with unique metabolic and genomic features linked to its distal nephron origin. This contrasts with the genomic complexity and aggressive clinical behavior observed in KRAS-mutant PRCC and URCC, highlighting the need for subtype-specific diagnostic criteria and therapeutic strategies.

This study analyzed 321 tumor samples from 244 Chinese patients with genitourinary cancers using targeted NGS. Distinct mutational landscapes and PD-L1-associated genes were identified across bladder, renal, and prostate cancers. Comparative analysis with Western cohorts revealed population-specific genomic heterogeneity, supporting region-tailored precision oncology.

After adjusting for potential confounders, the prognosis of patients with liver metastases remained an independent risk factor for ICIs (HR: 1.67, 95% CI: 1.31-2.12). Liver metastasis may be an independent risk factor for advanced solid tumors treated with ICIs.

These data support RRAS Q87L and RRAS2 Q72L as bona fide lung cancer drivers and nominate RRAS/RRAS2-mutant tumors as candidates for pan-RAS-targeted therapeutics. Our findings provide a biologic rationale and preclinical evidence to inform molecular testing paradigms and to prioritize enrollment of patients with RRAS/RRAS2-mutant NSCLC into future clinical trials of pan-RAS inhibitors.

P1, N=22, Active, not recruiting, National Cancer Institute (NCI) | N=85 --> 22 | Trial completion date: Jun 2026 --> Nov 2026 | Trial primary completion date: Jun 2026 --> Nov 2025