What are some of the key findings, progress and discoveries you have made with your research to date – and how will this make a difference to patients with this disease?
In the last few years, the identification of cancer “driver” mutations or gene alterations in patient tumours, such as the gene rearrangement of ROS1, has resulted in a massive shift towards the personalisation of lung cancer treatment. In the event that a “druggable” mutation or alteration can be identified in a patient, there are now targeted anti-cancer therapies, known as tyrosine kinase inhibitors (TKI), that are directed specifically against these targets. Although use of these TKIs often leads to dramatic and prolonged responses in these patients, acquired resistance eventually ensues.
My research involved the high-resolution protein mapping of a rare ROS1 lung cancer cell line as it developed resistance to an anti-ROS1 targeted therapy (crizotinib). I developed this new resistant cell line by treating these ROS1 lung cancer cells with drugs (like how drugs would be given to patients in the clinic) for 21 months, where it became more than 50-fold resistant to crizotinib when compared with the untreated cell line. I then used latest-generation mass spectrometry, known as SWATH-MS, to examine the proteome (a collection of more than 2,500 proteins found in these cell lines) to see which specific protein levels changed when the cell line became drug resistant. Overall, we identified 266 key proteins that were different between the cell lines, which are involved in various roles in cellular development, assembly and organisation, and growth and proliferation of cancer cells.
This is the first time that scientists have been able to examine the protein changes in this rare lung cancer when these cells become resistant to crizotinib. We believe that comprehensive protein mapping using will increase the understanding of the biological mechanisms involved in the acquisition of TKI resistance, which is crucial for the development of strategies to overcome resistance in the clinic.
What do you hope to achieve with this research project?
We have also looked at a range of lung cancer cell lines with different mutations which have been made resistant to different targeted TKIs in the same way as in the work presented here and then analysed with SWATH-MS. We are building a protein map to help us understand exactly how these cells become resistant to commonly used TKIs. We hope that by identifying which critical proteins are involved in TKI resistance, we can examine these proteins in patients as they are undergoing targeted treatment in order to monitor them for emerging drug resistance. This would then help their doctors to decide the best course of action for the patient’s care, prior to the patient becoming completely resistant to the drug and allowing the cancer to progress further.
How important was the funding from Lung Foundation Australia to your work?
The funding from Lung Foundation Australia, partnered with the Roslyn Hogan Memorial Lung Cancer Fund, supported my attendance at the 2018 Australian Lung Cancer Conference (ALCC) in Sydney. I was so glad I was able to attend ALCC. Being a translational cancer researcher, my attendance at conferences like ALCC is crucial in making sure that I am performing lung cancer research that is relevant and answering the right clinical questions that our clinicians can apply in their patient care. Through attending ALCC, I was able to receive valuable feedback from clinicians, researchers, and patient advocates on my research, as well as gaining new insights into what areas of lung cancer research I could answer with my work.
Do you have a message for Lung Foundation Australia’s supporters?
It is only with research that we will cure cancer. Research is the key to finding answers to our vital questions about cancer – what causes cell damage, why cells turn cancerous, how cancer grows and spreads and how we can most effectively attack it. It is now very clear that we need to understand much more about how cancer works so we can design personalised treatments for patients to offer them a greater chance of a cure.
We already know the power of funding cancer research. For the last three decades, breast cancer has been the most common cancer affecting Australian women. Back in the late 1980s, the chance of surviving at least five years was on average 72%. Now, with advances in early detection and better treatments funded by large breast cancer-focused charities, most people survive breast cancer. If we as a community can come together and stand behind lung cancer research, we know we can make a difference.