Single-cell RNA seq-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma
Journal of hepatology. 2024 Under the direction of Sarah Cappuyns, a collaborative group of researchers from around the globe delved into the cellular mechanisms that influence the effectiveness or resistance to the dual therapy of atezolizumab and bevacizumab in patients with advanced hepatocellular carcinoma (HCC). Employing single-cell RNA sequencing, they identified gene expression patterns for 21 distinct cell phenotypes and subsequently analyzed 422 RNA samples from HCC patients who had undergone this combined treatment. The research uncovered two primary response profiles to the therapy: one immune-mediated, marked by an abundance of CD8+ T effector cells and pro-inflammatory CXCL10+ macrophages, and the other, non-immune, related to angiogenesis, as indicated by the lowered expression of the VEGF co-receptor neuropilin-1 (NRP1). They found that primary resistance was associated with an increase in immunosuppressive myeloid cells and the activation of the Notch pathway. The study characterized "Immune-competent" and "Angiogenesis-driven" molecular subgroups that correlated with improved overall survival rates among patients receiving the combination therapy, as well as a "Resistant" group. This molecular classification system may enable the stratification of patients according to their treatment outcomes and inform strategies to combat resistance, potentially leading to more targeted treatment approaches and enhanced survival rates for those with advanced HCC.DOI: 10.1016/j.jhep.2024.12.016
LKB1 inactivation promotes epigenetic remodeling-induced lineage plasticity and antiandrogen resistance in prostate cancer
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Fei Li. et al.
The study, conducted by Fei Li, Pengfei Dai, and Huili Shi along with their collaborators, delves into the role of LKB1 inactivation in prostate cancer, particularly its impact on lineage plasticity and antiandrogen resistance. Utilizing single-cell RNA sequencing and whole-genome bisulfite sequencing, the researchers uncovered a molecular mechanism linking LKB1 inactivation to androgen receptor (AR) independence, a critical factor in castration-resistant prostate cancer (CRPC). They discovered that LKB1 inactivation promotes AR-independent lineage plasticity and global DNA hypomethylation, which are associated with poor clinical outcomes. Notably, the study identified that pharmacological inhibition of TET enzymes and supplementation with S-adenosyl methionine (SAM) effectively suppress AR-independent prostate cancer growth. This finding suggests a potential therapeutic strategy targeting DNA hypomethylation in AR-independent CRPC. The research provides valuable insights into the epigenetic remodeling in prostate cancer and paves the way for developing novel treatments for patients with advanced disease.
DOI: 10.1038/s41422-024-01025-z
Editor & Reviewer: Yanwen Zhu
