AUTHOR=Li Ling , Hu Mengdi , Wang Tao , Chen Hongzhuan , Xu Lu 

TITLE=Repositioning Aspirin to Treat Lung and Breast Cancers and Overcome Acquired Resistance to Targeted Therapy

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01503

DOI=10.3389/fonc.2019.01503

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> The major limitation of targeted cancer therapy is development of acquired resistance. Intratumoral heterogeneity and coexist of multiple resistance mechanisms make combination therapies targeting one specific mechanism inefficient.</p><p><bold>Methods:</bold> Transcriptional signature obtained from GEO was used to reposition FDA-approved drugs to treat lung and breast cancers as well as overcome acquired resistance to EGFR TKIs in lung cancer and to tamoxifen in breast cancer via CMap. <italic>In vitro</italic> and <italic>in vivo</italic> models were used to examine candidate drugs for their anti-cancer and anti-resistance efficacy and underlying mechanisms.</p><p><bold>Results:</bold> We found that aspirin, the most commonly used drug, not only inhibited proliferation and promoted apoptosis of cancer cells, but also delayed and overcame acquired resistance to targeted therapy using <italic>in vitro</italic> and <italic>in vivo</italic> models. The underlying mechanism could be attributed to enhanced cancer stemness and activated NF-κB signaling in acquired resistant tumors, both of which were suppressed by aspirin and rendered resistant tumors more sensitive to aspirin.</p><p><bold>Conclusions:</bold> Our data identify aspirin as a potential candidate for combination therapy for lung and breast cancers.</p>