Small cell lung cancer (SCLC) is a recalcitrant cancer and likely due to environmental insults as nearly 90% of the patients have tobacco exposure. Chemotherapy is the standard of care but it rarely affects complete cures and drug resistance is common. While a vast number of clinical trials with both cytotoxic and molecularly targeted therapies have been conducted, no new agents for SCLC patients have reached oncology practices since the 1980s. Thus, there is a pressing need to identify novel

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... lecular targets and effective therapies. In this Perspective, an overview of the putative source cell for SCLC, the neuroepithelial cell, will be presented to aid in the selection of novel drug targets. In particular, neuroepithelial cells are chemosensory and mechanosensory in function, regulating responses to oxygen tension, carbon dioxide, pH, and stretch. A panopoly of secretory factors, both peptidinergic and adrenergic, are released and in numerous experimental systems, shown to communicate with efferent neurons. Because it would be expected that the components of signal transduction pathways active in such functions are intimately connected to cell survival, these proteins are potential drug candidates. One example would be the complex set of proteins residing in the nuclear envelope, the LINCs, (or linkers of the nucleo-and cytoskeletal complex) which provide physical and biochemical signals to and from the extracellular environment and the nucleus. Furthermore, cell-based high content screens are amenable to discovery efforts targeting LINCs.