Collaborative, years-long patient studies analyse the heterogeneity of tumours
Cancer Collaboration is the way forward as multiple teams work together on new studies of cancer. Some tumours have many different parts – can identifying which tumours are the most variable give us some prognostic information to guide treatment?
Having always had an interest in science, Medical Oncologist, Dr Jamal-Hanjani, initially studied physics before medicine. She took time out of her clinical training to do a PhD and has, for many years, worked partly in clinical medicine and partly in research. She now specialises in lung cancer and is involved in two major studies, TRACERx and PEACE.
Dr Jamal-Hanjani’s research looks at intra-tumour heterogeneity – the differences between one part of a tumour and another part of the same tumour. Centuries ago, pathologists looking down a microscope could see that not all parts of a tumour looked the same, but they had limited information about how those differences had evolved. The TRACERx study looks at tumour evolution in time, throughout the lifetime of a cancer, and in space, between different parts of the same tumour.
Patients consent for the study team to take multiple samples when their tumour is removed – by having access to this very fresh tissue, gene sequencing can be done in much more detail than has been possible in the past.
A tumour is not a uniform mass; different parts evolve over time
Dr Jamal-Hanjani explains that you can think of a tumour as a tree, made up of a trunk and branches. The trunk contains the genetic changes that occurred during the early development of a tumour and the branches are those that happened later on and affect only a smaller part of a tumour; however, it may be a small branch that drives the progression or recurrence of a cancer. Some tumours will have more or fewer branches than others.
TRACERx follows patients for seven years. Blood samples are regularly collected and examined for circulating tumour cells and DNA in the hope that new biomarkers might be found. These biomarkers could predict a recurrence before it can be seen on a scan, thus allowing treatment to start earlier than is currently possible.
Patients who have a recurrence of their cancer have a biopsy taken, so that it can be compared with the initial samples taken from the primary tumour. This can differ from usual practice as recurrences are generally treated as being the same ‘type’ of tumour as the original primary. Dr Jamal-Hanjani says that in the future, it may become more acceptable that patients have a new biopsy at the time of recurrence as this may change their treatment.
Analysis of the first 100 patients has shown that tumours with the most heterogeneity (i.e. more branches) in genetic abnormalities involving chromosomes, pose an increased risk of recurrence and may lead to patient death. If the study can develop tests to show which tumours are the most heterogeneous, this may be able to guide future treatment in a way that isn’t possible today. Dr Jamal-Hanjani also hopes to find out the way in which chemotherapy affects the degree of heterogeneity, and how this might impact tumour evolution.
National post-mortem programme
PEACE is a national post-mortem programme, and so far many TRACERx patients have been recruited into the study. Patients who have metastatic disease from any type of cancer are consented for tissue collection after their death. These are difficult conversations to have; Dr Jamal-Hanjani says that she is humbled by how many patients want to contribute to a study from which they won’t personally benefit.
Tissue is collected from cancer tissue as well as normal tissue for comparison. Different teams use this data, working together rather than competing with each other – a collaboration that is not always the norm in the scientific world, where ‘publish or perish’ can be the motto. It is this collaboration, along with the longitudinal nature of studies like TRACERx and PEACE, which follow patients for many years, that will hopefully revolutionise the way we treat some cancers.
Dr Jamal-Hanjani says that she is mindful of the selfless willingness of patients to be part of cancer research, without which, studies such as PEACE would not exist, and from which she believes future patients will benefit.
Both TRACERx and PEACE are funded by Cancer Research UK. TRACERx is also funded by UCLH Biomedical Research Council, UCLH Experimental Cancer Medicine Centre and The Rosetrees Trust, and supported by the CRUK Lung Cancer Centre of Excellence, CRUK & UCL Cancer Trials Centre, the Francis Crick Institute and the UCL Cancer Institute.