Despite the success of tyrosine kinase-based cancer therapeutics, for most solid tumors the tyrosine kinases that drive disease remain unknown, limiting our ability to identify drug targets and predict response. Here we present the first large-scale survey of tyrosine kinase activity in lung cancer. Using a phosphoproteomic approach, we characterize tyrosine kinase signaling across 41 non-small cell lung cancer (NSCLC) cell lines and over 150 NSCLC tumors. Profiles of phosphotyrosine signaling are generated and analyzed to identify known oncogenic kinases such as EGFR and c-Met as well as novel ALK and ROS fusion proteins. Other activated tyrosine kinases such as PDGFRalpha and DDR1 not previously implicated in the genesis of NSCLC are also identified. By focusing on activated cell circuitry, the approach outlined here provides insight into cancer biology not available at the chromosomal and transcriptional levels and can be applied broadly across all human cancers.

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We describe traditional antimicrobial stewardship program (ASP) activities with a discussion of how these activities can be refocused in the setting of the COVID-19 pandemic. Additionally, we discuss possible adverse consequences of ASP attention diversion on COVID-19 response efforts and overall implications for future pandemic planning. We also discuss ASP in collaboration with other groups within health systems and how COVID-19 may affect these relationships long term. Despite the paucity of literature on Antimicrobial Stewardship and COVID-19, the potential contributions of ASPs during a pandemic are numerous. ASPs can develop strategies to identify patients with COVID-19-like-illness; this is particularly useful when these patients are missed at the time of health system entry. ASPs can also play a critical role in the management of potential drug shortages, developing local treatment guidelines, optimizing the use of antibiotics, and in the diagnostic stewardship of COVID-19 testing, among other roles. Importantly, it is often difficult to ascertain whether critically ill patients who are hospitalized with COVID-19 have concurrent or secondary bacterial infections-ASPs are ideally situated to help optimize antimicrobial use for these patients via a variety of mechanisms. ASPs are uniquely positioned to aid in pandemic response planning and relief efforts. ASPs are already integrated into health systems and play a key role in optimizing antimicrobial prescribing. As ASPs assist in COVID-19 response, understanding the role of ASPs in pandemic relief efforts may mitigate damage from future outbreaks.