Resistance mechanisms in lung cancer

The development of human cancers is a complex multistage process involving accumulation of both genetic and epigenetic alterations over time and this is particularly true with lung cancer. As a consequence, a single tumour is comprised of many different populations of cells with distinct genetic changes, known as tumour heterogeneity. Also, as a tumour progresses, some cells will continue to develop additional genetic alterations over time.

It is this tumour heterogeneity that is one of the main causes of therapy resistance and unfortunately the majority of patients will develop resistance during the course of their treatment. As such therapy resistance is a major challenge in oncology.

Based on response to the initial treatment, cancer resistance can be broadly classified into two categories, primary/intrinsic and acquired. Primary/intrinsic resistance is where the bulk of the tumour cells will already be resistant to a particular therapy, before it is given, making the therapy ineffective.

While primary drug resistance exists prior to any given treatment, acquired resistance occurs after initial therapy. Acquired drug resistance develops during the course of therapy where tumours that were initially sensitive begin to grow again. It can result from the therapy-induced selection of a resistant minor subpopulation of cells that was present in the original tumour.

Recent advances in understanding the molecular basis of cancer has led to an increase in our ability to determine the responsiveness of a tumour to a particular therapy. However, more research is needed to better understand the mechanisms by which cancer cells evade treatment. This will allow the development of therapeutic approaches to overcome therapy resistance.

Our researchers have already identified several new promising ways to reverse resistance which we hope will soon be ready for testing in the clinic.