BCL-XL PROTAC degrader DT2216 synergizes with sotorasib in preclinical models of KRASG12C-mutated cancers - Journal of Hematology & Oncology
Source : https://jhoonline.biomedcentral.com/articles/10.1186/s13045-022-01241-3
KRAS mutations are the most common oncogenic drivers. Sotorasib (AMG510), a covalent inhibitor of KRASG12C, was recently approved for the treatment of KRASG12C-mutated non-small cell lung cancer (NSCLC). However, the...
Conclusion/Relevance: We observed heterogeneous responses to sotorasib alone, whereas its combination with DT2216 strongly inhibited viability of KRASG12C tumor cell lines that partially responded to sotorasib treatment. Mechanistically, sotorasib treatment led to stabilization of BIM and co-treatment with DT2216 inhibited sotorasib-induced...
Direct Targeting KRAS Mutation in Non-Small Cell Lung Cancer: Focus on Resistance - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35267628/
KRAS is the most frequently mutated oncogene in non-small cell lung cancers (NSCLC), with a frequency of around 30%, and encoding a GTPAse that cycles between active form (GTP-bound) to...
Conclusion/Relevance: Small molecules such as sotorasib are now the first targeted drugs for KRAS G12C mutation, preventing conversion of the mutant protein to GTP-bound active state. Little is known about primary or acquired resistance. Acquired resistance does occur and may be due to genetic alterations in the nucleotide exchange function or...
A prognostic classification based on the International Association for the Study of Lung Cancer histologic grading and immunoscore in KRAS-mutant invasive non-mucinous adenocarcinoma - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35246953/
doi: 10.1111/1759-7714.14360. Online ahead of print. 1 Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China. 2 Department...
Conclusions:The Grading-Immunoscore classification refines the prognostic grouping of histological grading and might aid in the screening of potential candidates for immunotherapy in patients with KRAS-mutant adenocarcinoma.
PP6 deficiency in mice with KRAS mutation and Trp53 loss promotes early death by PDAC with cachexia-like features - PubMed
Source : https://pubmed.ncbi.nlm.nih.gov/35247012/
doi: 10.1111/cas.15315. Online ahead of print. 1 Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute, Natori, Japan. 2 Division of Cancer Molecular Biology, Tohoku University Graduate School of Medicine,...
Conclusion: Overall, Ppp6c deficiency in the presence of K-ras mutations and Trp53 gene deficiency promoted pancreatic tumorigenesis with generalized cachexia and early death. This study is the first evidence that Ppp6c suppresses mouse pancreatic carcinogenesis and supports use of Ppp6c-deficient cKP mice as a model for developing treatments...
targeted treatment options for the KRAS G12C mutation now approved in the UK
Revolutionary 'Death Star' Targeting Lung Cancer Drug Available on the NHS
Source : https://www.medscape.com/viewarticle/969575
A revolutionary life-extending drug has received approval from the National Institute for Health and Care Excellence (NICE) making it available on the NHS for patients with lung cancer. Following an...