NRAS G12S

P1/2, N=158, Active, not recruiting, Elicio Therapeutics | Recruiting --> Active, not recruiting

© 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

In addition to well-characterized MM drivers (KRAS, NRAS, etc.), 16 new candidate genes were found significantly mutated, including IKFZ3 (Aiolos), a transcription factor and direct target of degradation with lenalidomide therapy, harboring frameshift and stop-gain mutations in the protein dimerization domain which could affect complete differentiation of plasma cells...Conclusion These results highlight the power of genomic profiling in MM for early detection, discovery of novel drivers, monitoring of clonal selection and transformation to malignant disease. We show SMM is not a simple genomically-mature disorder, but rather a dynamic state with competing subclones, which could be leveraged for therapeutic interventions.

These findings argue against the development of 'early' resistance mechanisms after neratinib and pemetrexed exposure. Future studies will be required to understand how NSCLC cells become resistant to neratinib and pemetrexed.

Conclusions Molecular screening in non-BRAF PTC patients is useful to identify patients harboring RET fusions who may benefit from targeted therapies. As other potentially actionable gene fusions are also found in these patients, routine implementation of NGS analysis warrants a comprehensive biomarker study.

In this cohort with population-based and real-world patients, no differences in patient characteristics or treatment modalities were seen between different RAS mt, except a higher frequency of right-colon primaries among KRAS mt compared with NRAS mt. KRAS -G12S conferred a worse OS compared with some other KRAS mt, whereas no other differences in OS were seen. It therefore seems as if different RAS mt behave quite similar.

Our results highlighted a difference in the molecular profile of KRAS, NRAS,and BRAF mutations' distribution between metastatic colorectal cancer and non-metastatic ones: NRAS and BRAF mutations were associated with metastasis advent; moreover, the G13D mutation of KRAS was correlated to a better prognosis than mutations in codon 12 of KRAS: G12A and G12S alleles gave the worst prognosis.

Our findings suggest that KRAS may be mutated more frequently in OSCC compared to HRAS and NRAS. Also, the histological features of nuclear and cellular diameter differed significantly between the KRAS mutated and unmutated cases.

P1/2, N=156, Recruiting, Elicio Therapeutics | Not yet recruiting --> Recruiting

P1/2, N=156, Not yet recruiting, Elicio Therapeutics

RAS mutations could be useful in future target anti-EGFR therapy and molecular CRC screening strategy in Morocco.