Grant: Project Grant

Lung cancer is the most common cancer, killing 1.6 million people each year worldwide. Despite major progress in our understanding of the causes of lung cancer, over 85% of lung cancer patients still die within 5 years after diagnosis. This is due to lack of effective drugs or even "druggable" targets, or development of resistance to drugs after initial treatment, which results in spread of lung cancer cells to other parts of the bodies (metastasis). Therefore, there is an urgent need to determine what changes in the cell cause lung cancer spread and drug resistance, and find druggable targets. We and others recently discovered that certain changes in a number of genes which work together as a team, named "Hippo", are critical for the development and spread of lung cancers and their resistance to therapeutic drugs, suggesting that Hippo may be a good target for lung cancer. However, exactly how Hippo works in these processes is not completely known, and there are at present no drugs that can directly target Hippo for lung cancer therapy. Using state-of-the-art technologies, in this study we will fully decode the secret of Hippo-induced lung cancer formation, spreading, and drug resistance and finally develop novel Hippo-targeted drugs in preclinical lung cancer models. We will also combine Hippo-targeted therapies with other therapies (chemotherapy, targeted therapy, and immunotherapy) to test whether they potentiate one another's effect upon drug resistance or metastasis of cancers that are the most difficult to treat. Our research findings will not only establish Hippo as a druggable target for lung cancer, but also leads to effective therapeutic strategies for successful treatment of lung cancer.