Drug resistance

Cancer drug resistance is a major obstacle to achieving a cancer cure. Resistance to chemotherapeutic and molecularly targeted therapies can be intrinsic, dependent on the genetic makeup of the patient and/or involving molecular changes that have led to the development of the cancer. Drug therapies also provide strong evolutionary pressures on cancer cells, pressures which ultimately result in genetic, epigenetic and other molecular changes that promote adaptation of cancer cells to the therapeutic challenge, or selection for initially rare, intrinsically resistant cancer cells in a heterogeneous tumour cell population.

Understanding the cellular processes that drive cancer growth and invasion, as well as response and resistance to cancer drugs, is necessary for improving patient response to the diverse portfolio of available cancer drugs, for developing new therapies and for identifying biomarkers that enable tailoring therapies to individual patients, the concept which has been termed "personalised medicine".

Aims

Work in the Division of Cancer is aimed at understanding the genetic and epigenetic factors that drive cancer development and progression, to determine how these processes translate to cellular changes that drive resistance to chemotherapeutic drugs, such as platinum, anthracyclines and taxanes, as well as molecularly targeted therapies, primarily those that target the estrogen and androgen receptors in breast and prostate cancer. Using next generation sequencing, transcriptional profiling and biochemical approaches, we are elucidating the molecular and genetic landscapes of drug-responsive and resistant cancer, to identify key molecules and pathways that drive cancer cell survival, growth and metastasis. These findings are being translated to the development of biomarkers of response to cancer drugs and drug discovery for newly identified therapeutic targets.