Development and validation of a robust and sensitive HPLC-MS/MS method for the quantitation of MRTX849 in plasma and its application in pharmacokinetics
Source : https://pubs.rsc.org/en/content/articlelanding/2022/AN/D1AN01928G
MRTX849 is a novel, highly selective, targeted inhibitor of KRAS (G12C), which significantly improves the objective response rate in patients with advanced solid tumors. However, neither an analytical HPLC-MS/MS assay...
Relevance: MRTX849 is a novel, highly selective, targeted inhibitor of KRAS (G12C), which significantly improves the objective response rate in patients with advanced solid tumors. However, neither an analytical HPLC-MS/MS assay nor pharmacokinetics has been reported for MRTX849 in plasma. In the present study, chromatography was accomplished on...
ABCB1 limits brain exposure of the KRAS G12C inhibitor sotorasib, whereas ABCB1, CYP3A, and possibly OATP1a/1b restrict its oral availability - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35192958/
Sotorasib (Lumakras TM ) is the first FDA-approved KRAS G12C inhibitor for treatment of patients with non-small cell lung cancer (NSCLC) carrying this mutation. Using genetically modified mouse models, we...
Conclusion/Relevance: Collectively, the oral availability of sotorasib was markedly limited by CYP3A and possibly also by ABCB1 and OATP1a/b, whereas its brain accumulation was strongly restricted by ABCB1. The obtained results may help to further optimize the safety and efficacy of sotorasib in clinical use.
Concomitant KRAS mutations attenuate sensitivity of non-small cell lung cancer cells to KRAS G12C inhibition - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35177674/
The development of covalent inhibitors against KRAS G12C represents a major milestone in treatment of RAS-driven cancers, especially in non-small cell lung cancer (NSCLC), where KRAS G12C is one of...
Relevance: Overall, our study provides a comprehensive assessment of co-occurring KRAS mutations in NSCLC and in vitro evidence of the negative impact of co-occurring KRAS mutations on cellular response to G12C inhibitors, highlighting the need for a comprehensive KRAS tumour genotyping for optimal patient selection for treatment with a KRAS...
Transcriptomic Mapping of Non-Small Cell Lung Cancer K-RAS p.G12C Mutated Tumors: Identification of Surfaceome Targets and Immunologic Correlates
Source : https://www.frontiersin.org/articles/10.3389/fimmu.2021.786069/full
Targeting K-RAS-mutant non-small cell lung cancer (NSCLC) with novel inhibitors has shown promising results with the recent approval of sotorasib in this indication. However, progression to this agent is expected,...
Conclusion/Relevance: By interrogating massive datasets, including TCGA, we identified genes that code for surface membrane proteins that are selectively expressed in K-RAS mutated NSCLC and that could be used to vectorize novel therapies. Two genes, CLDN10 and TMPRSS6, were selected for their clear differentiation. In addition, we discovered...
This final decision expands eligibility for people with Medicare to get lung cancer screening with LCDT by lowering the starting age for screening from 55 to 50 years and reducing the tobacco smoking history from at least 30 packs per year to at least 20 packs per year.
CMS Expands Coverage of Lung Cancer Screening with Low Dose Computed Tomography | CMS
Today the Centers for Medicare & Medicaid Services (CMS) is announcing a national coverage determination (NCD) that expands coverage for lung cancer screening with low dose computed tomography (LDCT) to...