Human NSCLCs with activating mutations in EGFR frequently respond to treatment with EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib but responses are not durable as tumors acquire resistance. Secondary mutations in EGFR (T790M) or upregulation of the MET kinase are found in over 50% of resistant tumors. Here, we report increased activation of AXL and evidence of epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR-mutant lung cancer models with erlotinib acquired resistance in the absence of EGFR T790M or MET activation. Genetic or pharmacologic inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL, and in some cases its ligand GAS6, was found in EGFR-mutant lung cancers obtained from patients with EGFR TKI acquired resistance. These data identify AXL as a promising therapeutic target whose inhibition could prevent or overcome EGFR TKI acquired resistance in EGFR-mutant lung cancer patients.

Recent advances in electrodes for noninvasive recording of electroencephalograms expand opportunities collecting such data for diagnosis of neurological disorders and brain-computer interfaces. Existing technologies, however, cannot be used effectively in continuous, uninterrupted modes for more than a few days due to irritation and irreversible degradation in the electrical and mechanical properties of the skin interface. Here we introduce a soft, foldable collection of electrodes in open, fractal mesh geometries that can mount directly and chronically on the complex surface topology of the auricle and the mastoid, to provide highfidelity and long-term capture of electroencephalograms in ways that avoid any significant thermal, electrical, or mechanical loading of the skin. Experimental and computational studies establish the fundamental aspects of the bending and stretching mechanics that enable this type of intimate integration on the highly irregular and textured surfaces of the auricle. Cell level tests and thermal imaging studies establish the biocompatibility and wearability of such systems, with examples of high-quality measurements over periods of 2 wk with devices that remain mounted throughout daily activities including vigorous exercise, swimming, sleeping, and bathing. Demonstrations include a text speller with a steadystate visually evoked potential-based brain-computer interface and elicitation of an event-related potential (P300 wave).or more than 80 y, electroencephalography (EEG) has provided an effective noninvasive means to study human brain activity (1). EEG is instrumental in a wide range of clinical and research applications, from diagnosing epilepsy (2) to improving our understanding of language comprehension (3) and the development of brain-computer interfaces (BCI) (4). Conventional EEG recording systems, particularly the physical interface between the sensor (commonly known as an electrode) and the head, have limitations that constrain the more widespread use of EEG monitoring. Electrodes typically consist of rigid metal disks mechanically secured to the head with a mesh cap and chin strap, where electrolyte gels (5) enable efficient electrical coupling by reducing the impedance at the skin interface. This arrangement causes skin irritation (erythema) and leads to electrical degradation for periods of use that extend more than a few hours, typically caused by drying of the electrolyte gel (6). Recent technologies replace the gel (7, 8) with needles (8, 9), contact probes (10, 11), capacitive disks (12, 13), conductive composites (14, 15), or nanowires (16). Such dry electrodes have some promise, but they require multistep preparations, obtrusive wiring interfaces, and/or cumbersome mechanical fixtures. These shortcomings limit the potential for long-term use in diagnosis of neurological disabilities (17, 18) or in persistent BCI (17,19). For example, although microneedle electrodes can record EEG signals for a few hours (20), the interface does not offer the robustness, comfort, or eas...

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Non-invasive, biomedical devices have the potential to provide important, quantitative data for the assessment of skin diseases and wound healing. Traditional methods either rely on qualitative visual and tactile judgments of a professional and/or data obtained using instrumentation with forms that do not readily allow intimate integration with sensitive skin near a wound site. Here we report a skin-like electronics platform that can softly and reversibly laminate perilesionally at wounds to provide highly accurate, quantitative data of relevance to the management of surgical wound healing. Clinical studies on patients using thermal sensors and actuators in fractal layouts provide precise time-dependent mapping of temperature and thermal conductivity of the skin near the wounds. Analytical and simulation results establish the fundamentals of the sensing modalities, the mechanics of the system, and strategies for optimized design. The use of this type of ‘epidermal’ electronics system in a realistic, clinical setting with human subjects establishes a set of practical procedures in disinfection, reuse, and protocols for quantitative measurement. The results have the potential to address important unmet needs in chronic wound management.

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