Cancer
Structure of the helicase core of Werner helicase, a key target in microsatellite instability cancersWRN is a key drug target for cancers with microsatellite instability. A crystal structure of the helicase domain of WRN identifies its unique features and provides a basis for structure-guided design of inhibitors.
Myeloid transformation by MLL-ENL depends strictly on C/EBPThis publication shows that C/EBP (CCAAT enhancer–binding protein) transcription factors are mandatory for maintaining the myeloid leukemic phenotype, suggesting a therapeutic option by interfering with the non-oncogenic C/EBP dependence.
In vivo CRISPR/Cas9 knockout screen: TCEAL1 silencing enhances docetaxel efficacy in prostate cancerA whole genome in vivo CRISPR/Cas9 screen identifies TCEAL1 as a potential target to sensitise prostate cancer cells to docetaxel to improve the efficacy of chemotherapy.
Human G-MDSCs are neutrophils at distinct maturation stages promoting tumor growth in breast cancerThis study shows that immunosuppressive primary breast cancer patient–derived G-MDSCs (PMN-MDSCs) are neutrophils at a range of maturations stages, and provides in vivo evidence for that human G-MDSCs also promote tumor growth and myeloid immune cell exclusion.
The RECQL helicase prevents replication fork collapse during replication stressThis work shows that RECQL is an essential player in the protection of stalled replication forks and possibly the restart of broken replication forks, thereby representing a target for cancer therapy.
DDX5 promotes oncogene C3 and FABP1 expressions and drives intestinal inflammation and tumorigenesisIn intestinal epithelial cells (IECs), DDX5 promotes the expression of immune response genes and oncogenes posttranscriptionally and is a novel therapeutic target for treating colitis and intestinal cancers.
Thymosin α1 protects from CTLA-4 intestinal immunopathologyThis study demonstrates that Tα1 protects mice from anti–CTLA-4–induced colitis and sustains its antitumor activity, thus suggesting that Tα1 may be used in combination protocols.
Small molecule inhibitors and a kinase-dead expressing mouse model demonstrate that the kinase activity of Chk1 is essential for mouse embryos and cancer cellsThe study use small molecule inhibitors and a kinase-dead expressing mouse model to demonstrate that the kinase activity of Chk1 is essential for mouse embryos and cancer cells.
STAG1 vulnerabilities for exploiting cohesin synthetic lethality in STAG2-deficient cancersThis work highlights the degradation of STAG1 and inhibition of its interaction with cohesin as promising therapeutic strategies for exploiting synthetic lethality to treat STAG2-mutated tumors and lays the groundwork for the discovery of STAG1-directed small molecules.
Tradeoff between metabolic i-proteasome addiction and immune evasion in triple-negative breast cancerEngaging the immunoproteasome helps maintain proteostasis during TNBC development, but ultimately leads to increased immune visibility and favorable prognosis. Assessing i-proteasome expression could augment the prognostic and/or predictive value of TILs assessment in diagnostic practice.