Highlights of This Issue

Abstract

Uckermann and colleagues use infrared spectroscopy and present a translational approach for fast, label-free optical analysis of the IDH1 genotype of human glioma. Based on the initial research performed on cell lines and tumor cryosections, fresh glioma biopsies were classified regarding their IDH1 genotype with an accuracy of 86%. Because IDH1 mutations are early events in glioma formation with prognostic impact and most likely dichotomizing therapeutic decision making, analysis of the tumor's spectrome might be exploited to complement histopathology and molecular pathology for an in situ diagnostic screen.Clinical utilization of circulating tumor cells (CTC) as a biomarker has been limited by the low sensitivity of CTC assays. Myung and colleagues demonstrate that CTC capture can be improved through two innovative concepts: biomimetic cell rolling and nanotechnology-enabled multivalent binding capture. The investigators show that the new assay can capture high numbers of CTCs in a diverse cohort of patients. Moreover, CTC change is correlated with treatment response and disease status. These findings hold potential for clinical translation.Both EGFR and VEGF are validated targets for treatment of patients with metastatic colorectal cancer (mCRC); however, combinations of monoclonal antibodies targeting both pathways show disappointing results. Mésange and colleagues show that combinations of bevacizumab and erlotinib, a small molecule EGFR inhibitor, have activity in CRC models independent of RAS status and bevacizumab resistance. The results provide a molecular framework to better understand the increased activity of the bevacizumab-erlotinib combination, compared with bevacizumab alone, in the GERCOR DREAM phase III clinical trial. Differential activity of mAb and TKI targeting the same signaling pathway is likely applicable for other tumor types.Attempts at treating glioblastoma (GBM) patients with checkpoint inhibitors have failed to provide a survival benefit. A potential mechanism explaining the failure of PD-1 blockade is based on work showing that GBM-infiltrating T cells increase immunosuppressive indoleamine 2,3 dioxygenase 1 (IDO1) levels. Ladomersky and colleagues tested IDO1 inhibitor and PD-1 mAb treatment, with or without radiotherapy, and found that the combination of all three agents led to long-term survival in a substantial fraction of mice with intracranial GBM. These data provide rationale for the soon-to-open phase I/IIa clinical trial of simultaneous radiotherapy with PD-1 and IDO1 inhibition in GBM patients.