Non-Small Cell Lung Cancer from Genomics to Therapeutics: A Framework for Community Practice Integration to Arrive at Personalized Therapy Strategies
JOURNAL OF CLINICAL MEDICINE
Authors: Rajurkar, Swapnil; Mambetsariev, Isa; Pharaon, Rebecca; Leach, Benjamin; Tan, TingTing; Kulkarni, Prakash; Salgia, Ravi
Abstract
Non-small cell lung cancer (NSCLC) is a heterogeneous disease, and therapeutic management has advanced with the identification of various key oncogenic mutations that promote lung cancer tumorigenesis. Subsequent studies have developed targeted therapies against these oncogenes in the hope of personalizing therapy based on the molecular genomics of the tumor. This review presents approved treatments against actionable mutations in NSCLC as well as promising targets and therapies. We also discuss the current status of molecular testing practices in community oncology sites that would help to direct oncologists in lung cancer decision-making. We propose a collaborative framework between community practice and academic sites that can help improve the utilization of personalized strategies in the community, through incorporation of increased testing rates, virtual molecular tumor boards, vendor-based oncology clinical pathways, and an academic-type singular electronic health record system.
A Clickable APEX Probe for Proximity-Dependent Proteomic Profiling in Yeast
CELL CHEMICAL BIOLOGY
Authors: Li, Yi; Tian, Caiping; Liu, Keke; Zhou, Ying; Yang, Jing; Zou, Peng
Abstract
The engineered ascorbate peroxidase (APEX) is a powerful tool for the proximity-dependent labeling of proteins and RNAs in live cells. Although widely use in mammalian cells, APEX applications in microorganisms have been hampered by the poor labeling efficiency of its biotin-phenol (BP) substrate. In this study, we sought to address this challenge by designing and screening a panel of alkyne-functionalized substrates. Our best probe, Alk-Ph, substantially improves APEX-labeling efficiency in intact yeast cells, as it is more cell wall-permeant than BP. Through a combination of protein-centric and peptide-centric chemoproteomic experiments, we have identified 165 proteins with a specificity of 94% in the yeast mitochondrial matrix. In addition, we have demonstrated that Alk-Ph is useful for proximity-dependent RNA labeling in yeast, thus expanding the scope of APEX-seq. We envision that this improved APEX-labeling strategy would set the stage for the large-scale mapping of spatial proteome and transcriptome in yeast.