PhDs in Focus: Exploring beyond genetic defects in lung cancers
Welcome to our PhDs in Focus blog series, where our PhD students are showcasing their pioneering research projects at the National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre (BRC).
In this blog, Manchester BRC PhD student Matt Church outlines how their PhD project aims to better understand lung cancers without genetic defects to try to improve their outcome, as part of the Cancer Precision Medicine theme.
Lung cancer is the third most common cancer in the UK, but is responsible for the most deaths from cancer. This is due to the aggressive nature of the disease and because lung cancer is often diagnosed late and at an advanced stage. But can we improve the patient outcome in advanced lung cancer?
Hear more about Matt Church’s research and what advice he’d give to those thinking of applying to do a PhD
Lung cancer treatment
Thankfully in the last few decades, several excellent new drugs have been developed for lung cancer, in particular for non-small cell lung cancer which is the most common form of lung cancer. However, most of these drugs are only effective in a small proportion of cases who have been found to have specific defects in their cancer’s genetics, the DNA. Approximately half of non-small cell lung cancers have these genetic defects.
We have a good understanding of why lung cancers with genetic defects behave the way they do, and this allowed researchers to design drugs to specifically target the defects.
Having worked at The Christie NHS Foundation Trust as an oncology (cancer) doctor, the impact of lung cancer on patients and their family is clear.
Targeted drugs for lung cancers with genetic defects are generally very effective and have few side effects. So patients can continue to live the life they want despite their cancer such as playing golf, having holidays and looking after grandchildren.
However, in those without targetable genetic defects, treatments are limited to traditional chemotherapy and immunotherapy, which uses the immune system to attack the cancer. Sadly, less than half of lung cancers will respond well to these treatments and many patients struggle with side effects such as fatigue which impacts their life.
Lung cancers without genetic defects are much more common in those who have smoked, and so this is a particular problem in Greater Manchester, as the North West of England has particularly high rates of both smoking and lung cancer.
My research
My PhD research, funded by the National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre (BRC) and Medicines Discovery Catapult, aims to better understand these lung cancers without genetic defects to try to improve their outcome.
To do this, we will be recruiting patients from The Christie onto a research study to obtain biopsy samples of their cancer which we can analyse. Specifically, I will be looking at aspects of the cancer beyond DNA into other parts of the cancer – investigating the spatial biology of the disease, understanding how cells interact and the impact of their molecular profile, such as proteins, which are the action molecules of the cancer and RNA which controls cancer behaviour. We will also study how the cancer handles energy. If specific changes here can be identified, they could be targets for future drugs to treat cancer.
I will also be trying to identify markers or ‘fingerprints’ within the cancer which can tell us as doctors if a patient is likely to do well on a treatment or not. We know that tumours are complex ecosystems made up of the cancer itself but also the body’s immune defence and non-cancer tissue. I will be looking at this complex neighbourhood of tumours and the local immune system within them to see the impact of immunotherapy and markers of immunotherapy response.
These advanced methods will give a great deal of information about the cancer and, as researchers we know it can be difficult to know which bit of information is most important, which bits interact together and ‘see the wood for the trees’.
My research will involve not just finding the information, but trying to put it all together using computational techniques and machine learning to aim to better understand the disease and ultimately use it to help future cancer patients.