Amplification of EGFR and its active mutant EGFRvIII occur frequently in GBM. While EGFR and EGFRvIII play critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase inhibitors (TKIs) or antibodies has only shown limited efficacy in patients. Here, we discuss signaling pathways mediated by EGFR/EGFRvIII, current therapeutics, and novel strategies to target EGFR/EGFRvIII-amplified GBM.

T o date, hundreds of thousands of deaths have been attributed to coronavirus disease 2019 (COVID-19) 1. Millions of infections by SARS-CoV-2, the virus responsible for COVID-19, have been reported, although its full extent has yet to be determined owing to limited testing 2. Government interventions to slow viral spread have disrupted daily life and economic activity for billions of people. Strategies to ease restraints on human mobility and interaction without provoking a major resurgence of transmission and mortality will depend on accurate estimates of population levels of infection and immunity 3. Current testing for the virus largely depends on labor-intensive molecular techniques 4. Individuals with positive molecular tests represent only a small fraction of all infections, given limited deployment and the brief time window when real-time (RT)-PCR testing has the highest sensitivity 5-7. The proportion of undocumented cases in the original epidemic focus was estimated to be as high as 86% 8 , and asymptomatic infections are suspected to play a substantial role in transmission 9-14. Widely available, reliable antibody detection assays would enable more accurate estimates of SARS-CoV-2 prevalence and incidence. On February 4, 2020, the Secretary of the US Department of Health and Human Services issued an emergency use authorization (EUA) for the diagnosis of SARS-CoV-2 15 , allowing nucleic acid detection and immunoassay tests to be offered based on manufacturer-reported data without formal US Food and Drug Administration (FDA) clearance 16. In response, dozens of companies began to market laboratory-based immunoassays and point-of-care (POC) tests. Rigorous, comparative performance data are crucial to inform clinical care and public health responses.

Neural crest cells (NCC) are stem cells that generate different lineages, including neuroendocrine, melanocytic, cartilage, and bone. The differentiation potential of NCC varies according to the level from which cells emerge along the neural tube. For example, only anterior “cranial” NCC form craniofacial bone, whereas solely posterior “trunk” NCC contribute to sympathoadrenal cells. Importantly, the isolation of human fetal NCC carries ethical and scientific challenges, as NCC induction typically occur before pregnancy is detectable. As a result, current knowledge of NCC biology derives primarily from non-human organisms. Important differences between human and non-human NCC, such as expression of HNK1 in human but not mouse NCC, suggest a need to study human NCC directly. Here, we demonstrate that current protocols to differentiate human pluripotent stem cells (PSC) to NCC are biased toward cranial NCC. Addition of retinoic acid drove trunk-related markers and HOX genes characteristic of a posterior identity. Subsequent treatment with bone morphogenetic proteins (BMPs) enhanced differentiation to sympathoadrenal cells. Our approach provides methodology for detailed studies of human NCC, and clarifies roles for retinoids and BMPs in the differentiation of human PSC to trunk NCC and to sympathoadrenal lineages.