NRAS mutation

BRAF-mut PTC is associated with a pro-inflammatory TME milieu compared to BRAF-wt PTC. However, in this limited data set, treatment choice was not associated with differences in OS in BRAF-mut PTC.

The kinases PAK1 and PAK2 shield RAS from LZTR1-dependent degradation by phosphorylating T148, and targeting PAK1/2 activity improves RAS-directed therapy. Collectively, our findings reveal a novel regulatory circuit governing RAS stability that is preferentially active in blood cancers and potentially druggable.

P1, N=51, Completed, InxMed (Shanghai) Co., Ltd. | Active, not recruiting --> Completed | N=120 --> 51

This study provides an overview of the genomic landscape of early-stage nonsquamous NSCLC in Brazilian patients. The high prevalence of mutations observed in our cohort underscores the importance of genomic testing in this setting, enabling selection of patients suitable for targeted approved therapies or clinical trials.

Our study reveals the preliminary molecular landscape of Chinese pediatric sarcomas, indicating that molecular changes may represent different therapeutic responses and pathologic characteristics may correlate with molecular characteristics, suggesting the need for panel sequencing for pediatric sarcoma.

These data suggest the potential of the 6-gene Duplex Sequencing assay to improve EGFRi patient selection and therapeutic outcomes.

P2, N=59, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

Resistance to chemotherapy, particularly to first-line regimens such as FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), remains a critical barrier to successful treatment. Elevated baseline ctDNA levels and persistent TP53 mutations are associated with chemoresistance in colorectal cancer. Early reduction in ctDNA during therapy may serve as a robust predictor of response, supporting its integration into personalized treatment strategies.

The analysis included 29 patients who had previously received all standard therapies: fluoropyrimidines, oxaliplatin, and irinotecan (in a multi-agent regimen or sequentially) and bevacizumab (anti-VEGF therapy). In patients with tumors negative for KRAS, NRAS and BRAF mutations, cetuximab or panitumumab (anti-EGFR therapy) were also used...Only minor differences in survival outcomes were noted-likely due to real-world variability in patient characteristics and timing of treatment assessments. However, continued investigation of personalized and sequential treatment strategies that contain anti-angiogenic drugs is warranted to optimize outcomes.

Melanoma-private mutations in genes such as ARID1A, ARID2, PIK3CA, and CDKN2A indicated additional late events contributing to malignant progression. Overall, this study supports a model in which many melanomas evolve from pre-existing nevi through sequential acquisition and clonal amplification of somatic mutations, while also revealing heterogeneous evolutionary trajectories.

Using a doxycycline-inducible JAK2 knockout (KO) system, we validated JAK2 dependency in CBFA2T3::GLIS2 cell lines, observing impaired proliferation in vitro and in vivo and apoptosis induction in vitro. Both type I (ruxolitinib) and type II (CHZ868) JAK2 inhibitors showed selective in vitro activity in CBFA2T3::GLIS2-positive AML models...Both approaches converged on MAPK pathway activation as a resistance mechanism to ruxolitinib treatment. Combining ruxolitinib with MEK inhibitors showed a synergistic effect in cell lines and patient-derived xenograft (PDX) cells expressing the fusion and in vivo activity in a CBFA2T3::GLIS2 AML PDX, suggesting a potential approach to target this signaling circuitry in this poor outcome AML subtype.