Defining mechanisms of lineage transformation in lung cancer to combat resistance to targeted therapies

Lung cancer is the leading cause of cancer-related death in Canada. A major reason for the poor prognosis is the lack of effective drugs for treating advanced tumours.

New understanding of the mutations driving lung cancer has led to the development of targeted therapies that selectively inhibit mutated genes, leading to rapid cancer regression in specific subsets of patients. However, while these therapies improve patient survival and quality of life, they are not curative as all patients develop drug resistance.

While some causes behind this resistance have been defined, others remain elusive, and are becoming more prominent with newer generations of drugs. A major example is tumours changing how they look—shifting from one type of lung cancer to another—but what causes this is still not clear.

Dr. Inoue’s research will test whether treatment with targeted therapies creates the environment that allows tumours to “change their skin” and continue to grow in the presence of drugs. The goal is to determine the genes involved in this shift and prove they are responsible for drug resistance. This will lead to new therapeutic strategies that will provide longer-term survival benefits for lung cancer patients.