In This Issue
Cancer Discov February 1 2021 11 (2) 211-213; DOI:10.1158/2159-8290.CD-ITI11-2
Across cancer types, loss of heterozygosity at the locus encoding HLA-I was an independent prognostic factor for response to immune checkpoint blockade, and its predictive power improved when combined with measures of tumor mutation burden.
Lower airway dysbiosis characterized by excessive colonization with oral commensal microbes, particularly Veillonella parvula, was a predictor of poor prognosis in lung cancer, and in vivo experiments supported a role for V. parvula colonization in decreasing survival.
In a phase II clinical trial, personalized antibodies plus molecularly targeted chemotherapy improved median overall survival and the one-year survival rate in patients with gastroesophageal adenocarcinoma relative to historical survival data.
In patients with cholangiocarcinoma harboring FGFR fusions or rearrangements, response to the FGFR1–3 inhibitor was equally likely regardless of the type of genomic alteration, and resistance mutations affected the FGFR2 kinase domain.
Genetic analyses of healthy aged human epidermal cells revealed skin site–specific mutational signatures, with common skin cancer sites exhibiting more potentially oncogenic mutations and with high variability in mutations under positive selection among sites.
Organoids representing high-grade serous ovarian cancer were developed; these organoids exhibited varying sensitivities to chemotherapy drugs and elicited different immune responses, suggesting they may serve as a novel platform for discovery.
To address the inability of current high-grade serous tubo-ovarian carcinoma models to accurately recapitulate immunotherapy responses, a new mouse model was developed; proof-of concept experiments uncovered follistatin as a mediator of response.
The TLR3 ligand polyinosinic:polycytidylic acid improved the efficacy of chemotherapy observed in the context of FPR1 loss-of-function mutation, which occurs in 30% of individuals and diminishes the antitumor immune response following chemotherapy.
A hindrance to the study of metastasis via lymphatic vessels with lymph nodes as intermediate sites was overcome using a genetically engineered mouse model–derived allograft model, the use of which uncovered the Ang2–Tie2 pathway as a critical dependency.
The glutamatergic presynaptic protein Netrin-G1 was found to be a major contributor to the metabolic and immunosuppressive tumor microenvironment in pancreatic ductal adenocarcinoma, and blocking Netrin-G1 in vivo suppressed tumorigenesis.
In glioblastoma stem cells, YTHDF2 (which reads mRNA for the modified nucleotide N6-methyladenosine) stabilized MYC and VEGFA transcripts via an IGFBP3-mediated mechanism, and blocking IGF–IGF1R signaling in vivo hindered glioblastoma growth.
Liver-infiltrating leukemia stem cells in mice acquired a proliferative, chemotherapy-resistant phenotype characterized by overexpression of the gene encoding the lipase LIPG, which was sufficient to induce the same phenotype in non–liver-infiltrating leukemia cells.