Post-doctoral researcher Dr Lewis Quayle has spent his time in the laboratory of Professor Ingunn Holen (Department of Oncology and Metabolism, University of Sheffield) specialising in studies of dormant (non-dividing) breast cancer cells that survive chemotherapy and are responsible for breast cancer returning after treatment. Dr Quayle and Professor Holen have recently been awarded further funding from Against Breast Cancer for an 8-month project that will rely on their expertise in this area to study dormant breast cancer cells using advanced genetic methods and identify new strategies for their removal, thereby preventing breast cancer from returning.
Why are Non-Dividing Breast Cancer Cells a Problem?
Breast cancer claims nearly 12, 000 lives each year in the U.K. Around 2 out of every 10 patients experience that their breast cancer spreads (metastasises) and returns several years after they underwent surgery, chemotherapy and radiotherapy. We know that this is because some cancer cells escape from the breast tumour and settle in other parts of the body, usually the bone marrow, where they can survive for many years by becoming dormant (non-dividing) and remain undetected. In this dormant state, cancer cells are not sensitive to common chemotherapy drugs (which target dividing cells). At some point, the dormant cells can be triggered to start growing again and they can then cause spread to other organs such as the lungs, liver and brain.
Increasing Our Knowledge of Non-Dividing Breast Cancer Cells
To prevent breast cancer from returning, we need to first understand how cancer cells become dormant so that we can develop new treatments that eliminate the dormant cells responsible for the cancer coming back. In this project, we will use models previously developed by Dr Quayle, partly funded by an Against Breast Cancer seed grant, to specifically isolate the dormant breast cancer cells that survive treatment so we can study them further. We will use advanced genetic study methods along with computer-based analysis to study the genetic machinery of the surviving cancer cells (dormant cells) and compare this to that of those that are sensitive to chemotherapy (growing and dividing cells). This allows us to identify molecules that cancer cells “switch on or off” to become dormant and survive chemotherapy. We can then check if these molecules are present in human breast tumours that we know went on to spread (using information available in clinical databases), in order to select the most promising candidates for further study.
The results that we will gather during this project will pave the way for future projects where we can establish whether stopping these molecules from working (using genetic engineering or drugs) reduces the capacity of breast cancer cells to become dormant, thereby sensitising them to chemotherapy. Ultimately this work will allow us to develop new treatments to prevent breast cancer recurrence, benefiting a large number of patients whom have disease for which there is currently no effective (curative) treatment.
This project will be the culmination of a 5-year body of work that has aimed to develop novel models to study tumour cell dormancy and drug resistance. It is my hope that the results from this project will generate a number of promising candidates that could form the basis for the first generation of truly curative treatments for metastatic breast cancer.
Dr Lewis Quayle
Q&A, discussing preventing metastatic disease by targeting breast cancer cells that survive chemotherapy.
As part of our regular Research Q&A series, Dr Quayle took the time to answer questions about his research which were posed by supporters of Against Breast Cancer.
We are incredibly grateful to Against Breast Cancer for their generous support of our work, allowing Dr Quayle to develop a very exciting project in an area of unmet clinical need. To improve outcome for patients, it is essential that we prevent disease recurrence and spread. This, in turn, relies on understanding how we can disrupt the processes that cancer cells use become dormant and avoid detection and elimination.
Professor Ingunn Holen
Dr Quayle completed his B.Sc. in Biomedical Science with first class honours in 2013 for which he was awarded the IBMS President’s Prize and the Royal Society of Biology Award for academic excellence. Having completed his MRes in Medical and Biomedical Science the following year, he then went on to study for his Ph.D. in the Department of Oncology and Metabolism under the supervision of Professor Ingunn Holen and Dr Penelope Ottewell, which he was awarded in November 2017. He has since been working as a post-doctoral research associate in the Holen lab studying dormant, chemotherapy-resistant breast tumour cells using a combination of laboratory and advanced computational techniques.
Outside of work Dr Quayle is a dedicated rock climber, mountaineer and fell runner. This year Dr Quayle and his regular climbing partner will be completing an unsupported back-to-back dual traverse of the Welsh 3000s challenge in order to raise funds and support for Against Breast Cancer. This incredible challenge will see the pair attempt to traverse all 15 peaks above 3000ft in North Wales twice in a 48 hour period, covering over 60 miles and ascending (and descending) approximately 8000m in the process, all while carrying all the supplies and equipment that they will require. The route they intend to cover will require extended periods of fell running and several sections of rock climbing without additional protective equipment.