NRAS G12

HRAS p.G13R induced strongest molecular changes suggesting most serious pathobiological consequences, and HRAS p.G12S and p.G12V predominantly interfered with cellular signaling. Taken together, our data underscore the existence of HRAS variant-specific qualities of dysregulation and describe a differential pathophysiological architecture of HRAS-associated phenotypes.

P=N/A, N=9, Terminated, University Hospital, Bordeaux | Completed --> Terminated; Target number of inclusion not reached

After ruxolitinib therapy, he later developed leukocytosis and 2% circulating blasts. Repeat marrow demonstrated ≥ 15% ring sideroblasts. Retrospectively, the initial biopsy fulfills ICC 2022 criteria for MDS/MPN-SF3B1-T, highlighting the diagnostic value of genetics-integrated classification in fibrotic marrows.

Moreover, FTY720 co-treatment resensitized G12D NRAS-mutated M14(R)701 cells to gilteritinib in vivo. Co-treatment inactivated ERK, transcriptionally downregulated SPHK1, and inactivated downstream AKT, p70 S6K and BAD, with inactivation abrogated by constitutive SPHK1 expression. The clinically applicable S1PR modulators fingolimod and mocravimod resensitize NRAS-mutated FLT3-ITD AML cells to FLT3 inhibitors, supporting potential clinical efficacy.

P3, N=590, Recruiting, Revolution Medicines, Inc. | N=420 --> 590

ProgEvo enabled inference of a molecular evolution model and integration of evolution-informed covariates into clinical prognostic frameworks, supporting the development of the IPSS-M-Evo model. A free web-based tool allows clinicians to calculate the IPSS-M-Evo score and match individual mutational profiles to cohort-derived evolutionary trajectories (https://evoclin.unimib.it/tools/evolution-graphs.html and https://evoclin.unimib.it/tools/ipssmevo.html). (Funded by the European Union and others.).

P1/2, N=5, Terminated, National Cancer Institute (NCI) | Completed --> Terminated; Study was closed due to lack of accrual and study outcomes overlapped with another protocol's eligibility.

P1, N=18, Not yet recruiting, Beijing DCTY Biotech Co.,Ltd. | N=110 --> 18 | Trial completion date: May 2028 --> Aug 2028 | Trial primary completion date: May 2028 --> Aug 2028

We report a rare case of HPV-associated sarcomatoid carcinoma of the base of the tongue. The predominance of spindle cell morphology combined with an atypical immunophenotype-lack of squamous markers and strong p16 expression-poses a significant diagnostic challenge, particularly in small biopsies. Comprehensive diagnostic evaluation, including HPV-specific testing such as in situ hybridization, is critical for accurate diagnosis.

P2, N=40, Recruiting, Zhejiang University

BBO-8520 exerted more potent and sustained inhibition of KRAS G12C and anti-tumor activity in vitro and in vivo compared with sotorasib, a KRAS G12C (OFF)-only inhibitor...Moreover, in some contexts, disruption of RAS-PI3Kα further increased the anti-tumor activity of BBO-8520 monotherapy. These results reveal mechanistic differences between KRAS (ON) and (OFF) inhibitors, highlight the importance of PI3Kα-AKT signaling in driving resistance to KRAS inhibition in lung cancer, and suggest combination strategies that suppress PI3Kα-AKT to improve the response to KRAS inhibitors.

P1/2, N=105, Not yet recruiting, Institut De Recherches Internationales Servier IRIS