Highlights of This Issue

Abstract

Recurrent malignant gliomas carry a poor prognosis, and targeted therapy is an area of active investigation. A noninvasive biomarker that accurately assesses the treatment response with prognostic value is critically needed. Schwarzenberg and colleagues examine the amino-acid-analogue L-3,4-dihydroxy-6-18F-fluorophenyl-alanine (18F-FDOPA) PET imaging in patients with recurrent high-grade malignant gliomas on antiangiogenic treatment with bevacizumab. This biomarker predicted treatment response successfully as early as 1 to 2 weeks after starting therapy and provided prognostic information. The results of the study can guide the selection of treatment for these patients by identifying responders from nonresponders at an early time after starting therapy.The identification of mutated tumor antigens, which have been found in many cases to represent the predominant targets of tumor-reactive T cells, remains a challenging and time-consuming process. In an attempt to streamline this process, Lu and colleagues developed a novel genetic strategy that involved the screening of tandem minigene libraries encoding nonsynonymous mutations identified by whole-exome sequencing. Use of this approach, which resulted in the identification of mutated antigens recognized by the two populations of melanoma-reactive T cells that were initially evaluated, may facilitate the development of new adoptive cell therapies that target mutated antigens.One of the immunotherapy approaches for cancer is the blocking of immunoinhibitory pair PD-1 and PD-L1 on the surface of lymphocytes and tumor cells. In a large panel of melanoma cell lines, Atefi and colleagues investigated the effect of targeted therapy drugs on expression of PD-L1 and provided indications that different mechanisms of resistance to the BRAF inhibitor vemurafenib may have differential effects on expression of PD-L1. Moreover, they provided evidences for combinatorial effects of targeted and immune therapy by indicating the paradoxical effect of vemurafenib on restoring activity of the MAPK pathway and cytokine production in PD-L1 exposed lymphocytes.The development of new drugs and the evolution of mutations that lead to treatment resistance both require longitudinal response assessment. Accurate assessment can decrease exposure to the toxicities of futile treatments and speed access to beneficial alternatives. Zhao and colleagues characterized variability in measuring tumor change on CT in patients with metastatic colorectal carcinoma. They found that computer-aided analysis produced total system variability of 11% for longest diameters, 19% for bidimensional measurements, and 22% for whole tumor volumes. Any changes exceeding these values are likely to be biologically meaningful and can serve as indications to refine patient management.