Highlights of This Issue

Abstract

EGFR is one of the major growth factor receptors to which broad ranges of cancers are addicted for growth and survival. Lim, Yoo, and colleagues introduced GC1118, a novel EGFR-targeted antibody with different binding epitopes and strong inhibitory activities to high-affinity EGFR ligands. GC1118 demonstrated robust antitumor activity on colorectal tumor xenografts with elevated expression of high-affinity ligands while cetuximab did not. Considering the clinical implications of high-affinity EGFR ligands in metastasis and resistance to current anti-EGFR therapeutics, GC1118 would be another therapeutic option for refractory cancer patients.Triple-negative breast cancer (TNBC) is a recalcitrant malignancy. Since TNBC lacks expression of ER, PR, and Her2 receptors, it is difficult to develop personalized therapies. In this study, Paulmurugan and colleagues tested the efficacy of orlistat, an antiobesity drug, as a novel repurposed drug against TNBC. The orlistat delivered by folate receptor–targeted HEA-b-EHA polymeric micellar nanoparticles improved the solubility, bioavailability, and therapeutic efficacy of orlistat in vitro and in vivo. The results of this study indicate that orlistat packaged in HEA-b-EHA micellar-NPs is a highly promising new drug formulation for TNBC therapy.Interference with endothelial metabolism is a promising, yet unexploited strategy for angiogenesis inhibition. Endothelial cells are exquisitely sensitive to 2-deoxy-D-glucose (2-DG), a glycolysis and glycosylation inhibitor. In this report, Kovács and colleagues provide important mechanistic insight by linking 2-DG's interference with N-linked glycosylation with endothelial selective downregulation of growth factor–induced AKT and ERK phosphorylation, as well as ER stress–induced endothelial apoptosis via GSK3B activation. These findings uncover the potential of targeting critical angiogenesis pathways by modulation of endothelial metabolism as a novel strategy to inhibit angiogenesis and overcome resistance to currently available antiangiogenic agents.Novel cancer-specific cell surface biomarkers are needed to empower direct therapeutic tumor targeting. Human leukocyte antigens (HLA) present peptides derived from the cancerous protein repertoire, creating distinct cell surface complexes through which T cells naturally recognize and target ovarian tumors. Here, Patterson and colleagues used proteomics to identify a macrophage migration inhibitory factor (MIF)-derived peptide presented by the HLA of ovarian cancer cells. An antibody specific for this HLA/MIF complex then selectively stained ovarian tumors but not normal fallopian tube, and exhibited tumoricidal activity when toxin conjugated. These results suggest that HLA/MIF is a potential therapeutic target for ovarian cancer.