The molecular basis of cancer development and drug resistance

Lead researcher

Dr Walter Fairlie

Dr Walter Fairlie

Olivia Newton-John Cancer Research Institite, La Trobe University, Walter and Eliza Hall Institute of Medical Research

Tumour type:
All cancers

Years funded

Project description

All cells within our body possess the ability to kill themselves when required, for example, when they become damaged. This process is known as apoptosis and is essential for us to remain health. However, defects in apoptosis can arise that prevent the cells from dying and this can lead to cancer.

In addition, these defects make cancer cells difficult to kill using approaches such as chemotherapy. How apoptosis is controlled within cells is a major question in biology. While we know it involves a family of proteins called the 'Bcl-2 family' it is not well-understood how these proteins interact with each other to dictate the fate of a cell which interactions are important for cancer development and cancer drug resistance.

In our project we use a unique set of reagents we have developed to establish which members of the Bcl-2 family are critical in cancer development and which interactions are most important for determining responses to chemotherapy and other drugs. 

What is the need?

In order to better understand how to prevent cancer, it is important to determine the molecular basis of how it develops and our research, in part, aims to address this question.

As many cancers fail to respond - or respond poorly, to treatment, it is also valuable to gain insights into the molecular reasons underlying this drug resistance, as this information could potentially inform alternative treatment options.

This is becoming an increasingly important issue as new drugs have been developed that can specifically target the Bcl-2 proteins within cells. Whilst these drugs have now been approved for use in patients with certain cancers and have been shown to be extremely effective, other types of cancers show little or no response because the drugs fail to induce appoptosis of the cancer cells.

If we can understand which molecules are involved in this process of cell death, and how these molecules interact with each other, we can being to develop strategies to increase drug effectiveness.  

What is the impact of this research?

If successful, this research will provide greater insight, at a molecular level, into how cancer develops and why certain cancers respond better than others to treatment.

Indeed, our studies have already provided important advances in our understanding of one of the main processes (apoptosis) that often becomes defective in cancer cells. In addition, we have also shown that there is one critical interaction between the key molecular players involved in this process that dictates the effectiveness of some treatment options.

By improving our understanding of how cell death works, we'll be better equipped to develop new prevention and treatment strategies. 

"By improving our understanding of how cell death works, we'll be better equipped to develop new prevention and treatment strategies ."