In This Issue
Cancer Discov December 1 2020 10 (12) 1775-1779; DOI:10.1158/2159-8290.CD-ITI10-12
In patients with non–small cell lung cancer, local recurrence following radiotherapy was predicted by loss-of-function KEAP1 mutations or gain-of-function NFE2L2 mutations, and this resistance could be overcome by glutaminase inhibition.
Patients receiving immune checkpoint blockade therapies who had lower circulating tumor DNA (ctDNA) variant allele frequencies on treatment compared with pretreatment had a higher objective response rate and improved overall survival, suggesting that ctDNA analysis may complement existing prognostic techniques.
In patients with acute myeloid leukemia receiving memory-like natural killer (NK)–cell therapy, expression of the inhibitory immune checkpoint receptor NKG2A by the memory-like NK cells was associated with lack of treatment response.
Preventing glycosylation of the immuno-suppressive transmembrane protein B7-H4 increased its ubiquitination and subsequent degradation, and inhibition of B7-H4 glycosylation in vivo improved immunogenicity of immune-cold tumors.
In vitro and in vivo experiments using models of acute myeloid leukemia showed that the folate cycle enzyme MTHFR mediated response to BET inhibitors, which target oncogenic MYC expression and are in phase I and II clinical trials.
In genetically engineered mouse models, loss-of-function mutations in Kmt2d, which encodes a histone methyltransferase often mutated in human cancers, led to increased anti–PD-1 efficacy against a variety of cancer types.
Mutations that drive acute myeloid leukemia, especially in combination, induced epigenetic alterations prior to leukemogenesis, resulting in epigenetic diversity that was associated with poor prognosis in patients.
A new method coupled identification of protein–protein interactions and synthetic-lethal relationships to reveal previously unknown and functionally relevant RAS pathway interactors in mutant KRAS–driven lung adenocarcinoma models.
G34W mutation in histone 3.3, found in most cases of giant cell tumor of bone, caused large-scale epigenetic remodeling that led to aberrant differentiation and recruitment of the giant osteoclasts that underlie the pathologic features of this tumor type.