Highlights of This Issue

Abstract

Raja and colleagues explored changes in levels of ctDNA in advanced/metastatic NSCLC and UC patients receiving the anti-PD-L1 monoclonal antibody durvalumab. Reduction in ctDNA levels at 6 weeks was associated with RECIST responses, PFS and OS, and often preceded RECIST response. Thus, early changes in ctDNA may predict long-term benefit from immunotherapy and enable treatment decisions, particularly in indications in which assessing radiographic responses may be difficult.Mesothelioma is an aggressive cancer with limited treatment options and often with resistance to immunotherapy. To overcome resistance to previous treatments, Tallón de Lara and colleagues showed that the synergy of gemcitabine and immune checkpoint inhibitors (ICI) outperformed single treatment in a preclinical mouse model of mesothelioma. Two patients with mesothelioma, who did not respond to the single treatments, responded to the combination when given. Interestingly, dexamethasone, widely used in the clinics to treat side effects, dampened the response in the preclinical model. This study gives a new rationale to combine ICI and gemcitabine in mesothelioma patientsPatients with leukemia can develop bone defects (osteonecrosis) in hip bones, which can lead to joint collapse. A new treatment involves drilling a track in the affected bone (decompression surgery), aspirating marrow cells from the pelvis and implanting them into the bone defect. To visualize the cells, the authors treated patients with an iron supplement 1 to 2 days before the surgery. The cells in the bone marrow took up the iron. When iron-loaded cells were then harvested from the bone marrow and transplanted in the bone defect, they could be detect with MR imaging. This new stem cell imaging approach may help to better understand and optimize stem cell therapies.TRC105 is a neutralizing antibody targeting the TGF-β coreceptor endoglin and is currently being tested in clinical trials as antiangiogenic therapy. TRC105 prevents binding of BMP-9 to endoglin, which controls (tumor) angiogenesis. Paauwe and colleagues show that endoglin also is expressed on cancer-associated fibroblasts (CAFs) and reveal a role for this receptor in CAF invasion. TRC105 treatment reduced invasive capacity of CAFs in vitro and metastatic spread of CRC in vivo. This underlines the potential of TRC105 to be more than a “classic anti-angiogenic drug,” targeting both endothelium and CAF, thereby limiting metastatic spread on multiple levels.