Drug Discovery for Atypical Pulmonary Carcinoid Using a Library of Targeted Agents

摘要: BACKGROUND: On average it costs~ $1 billion and takes> 15 years to develop a new drug; this is a major challenge to drug discovery for rare forms of lung cancer like atypical pulmonary carcinoid. One way to overcome this challenge is to identify existing drugs active against multiple types of neuroendocrine lung cancers.METHODS: We created a library of 292 targeted agents that inhibit 104 different cellular pathways, including drugs that are FDA-approved (31 drugs, 11%), in phase III (29 drugs, 10%), phase II (51 drugs, 18%), or phase I (30 drugs, 10%) clinical trials or in pre-clinical drug development (150 agents, 51%). We screened this collection on a panel of pulmonary neuroendocrine tumor cell lines: atypical carcinoid (NCI-H720 and H835) and small cell lung cancer (G1C, H69).RESULTS: Navitoclax, which targets Bcl-2/BCL-XL, showed potent inhibition against NCI-H720 vs. NCI-H835 (IC50= 66 and …