Highlights of This Issue

Abstract

Detection of signals of micrometastatic disease in early breast cancer may improve risk stratification, and serum metabolomic profiles of early breast cancer patients have been shown to be predictive of relapse in a single institution series. Taking samples from a multicentre, phase III adjuvant breast cancer trial in premenopausal women, Hart and colleagues used NMR spectra of preoperative serum samples to build a model that identified women at higher risk of relapse, independent of standard risk factors. Metabolomic analysis has the potential to improve disease staging and prognostication and allow better tailoring of adjuvant therapies.MERTK tyrosine kinase is a potential therapeutic target in acute leukemia. DeRyckere and colleagues developed a series of novel, orally bioavailable MERTK-selective tyrosine kinase inhibitors and now report robust activity mediated by UNC2025, a third-generation compound suitable for clinical development in preclinical acute leukemia models. UNC2025 had antileukemia activity in approximately 30% of 260 freshly isolated leukemia patient samples and had therapeutic activity alone and in combination with cytotoxic chemotherapy in cell line and patient-derived xenografts, suggesting that a large fraction of patients with acute leukemia could benefit from treatment with a MERTK-targeted therapy.CD38 expression is associated with poor prognosis in chronic lymphocytic leukemia (CLL). CD38 is an ectoenzyme that cooperates in migration, adhesion, and invasion through its association with CXCR4, MMP9, and CD49d. To explore its potential as a drug target in CLL, Matas-Céspedes and colleagues analyzed the effect of the anti-CD38 monoclonal antibody daratumumab. The authors demonstrate a dual effect of daratumumab by erradicating the tumor cell both in vitro and in vivo, and by hampering CLL cell adhesion, migration, and homing to secondary organs. These results provide scientific rationale for the use of daratumumab in poor prognosis CD38+CLL.The role of neutrophils in the tumor microenvironment remains controversial. To explore their role in gastric cancer development, Li and colleagues analyzed the distribution and clinical relevance of neutrophils in different microanatomical areas and peripheral blood and assessed the regulation and function of neutrophils by both in vitro and in vivo studies. Their results provided direct evidence supporting the pivotal role of IL-17+ neutrophils in promoting angiogenesis during gastric cancer progression and revealed a fine-tuned collaboration between cancer cells and immune cells in distinct tumor milieus, potentially providing future therapeutic avenues against cancer.