World CUP Week: Researchers are screening hundreds of tumour genes in search of drug targets that could open the door to more personalised cancer care
Most cancers are named – and treated – according to where the first tumour is found. But for some patients, tumours are detected in various organs of the body but the origin of the disease remains a mystery.
People with Cancer of Unknown Primary (CUP) are up against it. Their disease is advanced at the time of diagnosis and there are no specific treatment options available. As time is of the essence, they are usually offered several drugs at once – an approach known as polychemotherapy – in the hope that one of them may work. The outcomes are often poor and therapies affecting all of the body’s cells can make patients feel very unwell.
‘We would like to see a more personalised approach to therapy in patients with CUP,’ explained Dr Manel Esteller, Director of the Josep Carreras Leukaemia Research Institute (IJC) in Barcelona. ‘For common cancer types, such as colon cancer and lung cancer, some hospitals screen patients for genes which help them select a targeted therapy. In CUP, we don’t yet know which genes to look for.’
To rectify this, Dr Esteller is running the CUPP-On project which will analyse samples from 50 patients with CUP. The team are looking for up to 500 genetic mutations or copy number variations (CNV) frequently observed in solid tumours, for which there are already approved therapies available.
‘In selected cases, we will take a sample of the patient’s tumour and grow it in mice where we can then test existing therapies to establish whether it reduces tumour growth,’ Dr Esteller said.
Clinicians may consider using this information to change their patients’ treatment plan. Looking at the bigger picture, the study could offer clues about the origins of CUPs. ‘Is the original tumour small or hidden? Is there something special about these tumour types? Are certain genes responsible for a proportion of CUP cases? We hope to find out,’ said Dr Esteller.
Other advances could flow from the project, such as the inclusion of CUP patients in so-called basket trials where patients are recruited to clinical studies based on having a tumour with a specific mutation which can be targeted by a drug.
‘Basket trials don’t care about tumour type or location – they include patients based on the presence of certain mutations,’ Dr Esteller said. ‘If we show that some CUP patients have mutations that are actionable by a drug, it becomes possible to join these kinds of trials.’
He said targeted therapy also brings benefits beyond survival as treatment tends to be well tolerated, helping to preserve quality of life. If the study proves successful, the results could be translated into clinical practice relatively swiftly as the drugs are already approved for human use. What’s more, as the cost of gene sequencing is much lower than it was a decade ago, there are fewer barriers to access in hospitals with sufficient lab capacity.
The CUP-On project is supported by the Sarah Jennifer Knott Foundation, a charitable organisation devoted to promoting awareness, education and research of CUP. ‘Support from charitable foundations is critical right now as it can be challenging to attract large grants from public agencies for rare tumours,’ Dr Esteller said. ‘Foundations can make a big difference by jump-starting research initiatives like this one.’
Tanya Knott, Director of the Sarah Jennifer Knott Foundation said patients diagnosed with cancer of unknown primary desperately need greater access to genomic profiling and potential targeted treatments. ‘The potential diagnostic and treatment opportunities that Dr Esteller’s research study will bring for CUP patients is incredible and we feel honoured to contribute to his amazing work.’
World CUP Awareness Week runs from 20-26 September 2021