NRAS Q61L

However, parity decreased the overall prevalence of tumors bearing Krasmut, and the magnitude of this decrease depended on both the number and timing of pregnancies. These multistage models may be useful for elucidating biological features of premalignant mammary neoplasia.

Additionally, CT2A-luc demonstrated substantial baseline secretion of the CCL-2, CCL-5, and CCL-22 chemokines, which play important roles as myeloid chemoattractants. Although the clinical contexts that can be modeled by GL261 and CT2A for huGBM are limited, CT2A may be an informative model of immunotherapy resistance due to its deficits in antigen presentation machinery and interferon response pathways.

RMC-7977 is a potent, oral small molecule inhibitor of both wild-type and mutant GTP-bound RAS oncoproteins (RASMULTI) and is a preclinical tool compound representative of the clinical candidate RMC-6236, currently in clinical evaluation (NCT05379985)...Gilteritinib and the gilteritinib/venetoclax combination selected for survival of cells harboring NRAS mutations, but RMC-7977 inhibited outgrowth of all cell populations...In vivo studies investigating the tolerability and activity of RMC-7977 and RMC-7977 combinations in RAS mutant/FLT3i-resistant patient-derived xenograft models are ongoing and will be presented. Collectively, our data provide preclinical evidence that combination therapies leveraging RASMULTI(ON) inhibition are effective in suppressing RAS-mutant AML clones, a common mechanism of resistance to currently approved targeted therapies in AML and a current area of high unmet clinical need.

Primary limitations include the total quantity of single cells and breadth of available genomic subtypes plus inherent noisiness of the applied methodologies. Nonetheless, these findings nominate novel, testable therapeutic targets.

We found that all 23 CAAs showed diffuse and strong membranous RAS Q61R immunoreactivity (100% sensitivity), while none of the 8 OSCCs showed immunoreactivity (100% specificity). The data supports the use of RAS Q61R-specific rabbit monoclonal antibody for diagnostic IHC confirmation of CAA and ruling out OSCC in dogs.

Even focal expression of a melanocytic marker should cast doubt on a diagnosis of PDS and raise the possibility of de-differentiated melanoma, since therapy and outcomes are significantly different. Poster type: Poster Defense

P1/2, N=39, Completed, Gritstone bio, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Mar 2023 | Trial primary completion date: Dec 2023 --> Mar 2023

Each OSUMMER cell line possesses distinct in vitro growth properties, trametinib sensitivity, mutational signatures, and predicted antigenicity. Analysis of OSUMMER allografts shows a correlation between strong, predicted antigenicity and poor tumor outgrowth. These data suggest that the OSUMMER lines will be a valuable tool for modeling the heterogeneous responses of human melanomas to targeted and immune-based therapies.

Regimen was switched to oral Binimetinib 45 mg daily for advanced NRAS mutant melanoma...Immune checkpoint inhibitors Pembrolizumab, Ipilimumab and Nivolumab are the most common immunotherapeutic agents used for mucosal melanomas. More recently Talimogene Laherparepvec (T-VEC) intra-lesional therapy is used to invoke local immune response which has promising results. Rapid progression of mucosal melanomas require early detection and intervention to prevent metastasis and recurrence however overall survival rate is not affected.

NRAS mutated melanoma has been shown to respond to treatment with the MEK-inhibitor binimetinib, however the PFS of 2,8 months and the median OS of 11 months was not promising [1]. Three patients with high tumor load all benefitted from treatment with trametinib and showed a explicitly longer PFS than the published data. After progression on ICB we therefore recommend to consider MEK-inhibition for NRAS mutated melanoma in selected cases.

P2/3, N=8, Terminated, The Christie NHS Foundation Trust | N=1050 --> 8 | Trial completion date: Oct 2030 --> Jan 2023 | Recruiting --> Terminated | Trial primary completion date: Oct 2030 --> Jan 2023; Closed earlier than expected due to the need for a redesign to reflect the recent change in standard of care guidelines. New design will include these treatments.