Scientists discover how lung cancer spreads towards end of life

The scientists examined the full DNA sequences of metastasised or spread lung cancers. Many of them looked very different to the DNA sequence of the primary tumour due to large numbers of mutations and changes to their chromosomes. These differences may have made it easier for more metastases to generate and spread, even after earlier successful treatment in some cases.  

As they metastasise, lung cancer tumours undergo significant changes to their genetic make-up. They have large numbers of mutations and can also undergo changes to their chromosomes, such as losing or gaining copies of chromosomes.

Together, these changes make it easier for lung cancer to survive, spread and resist treatment. In the study, which was published in Nature, over half of metastasised lung cancer tumours seeded further tumours to increase the cancer’s spread.

The researchers hope that this better understanding how tumours change as they spread will help them find treatments that can stop advanced lung cancers from further metastasizing.

Clinical Lecturer at UCL and first author of the study, Dr Sonya Hessey (UCL Cancer Institute), said: “If we want more people to survive lung cancer, we need to stop it from progressing to advanced stages and spreading to other parts of the body. Cancers which have spread are by far the hardest to successfully treat, and lung cancer is especially difficult as a very high number of people with the disease see it come back even after treatment.

“Our research shows that metastasised lung tumours directly produce more tumours. Each time a metastasis seeds another metastasis, they look increasingly different to the cancer that they came from. If we can target these different metastatic tumours, we can slow lung cancer down or even stop it from progressing further.”

The research included people who took part in two Cancer Research UK-funded studies called TRACERx and PEACE. The TRACERx study follows people diagnosed with lung cancer to see how it evolves and responds to treatment throughout their lives whereas the PEACE study looks at the final stages of life with cancer by analysing tumour samples taken after death with informed consent.

Chief Investigator of the PEACE study, Professor Mariam Jamal-Hanjani (UCL Cancer Institute), said: “The TRACERx and PEACE studies are delivering remarkable insights into how cancer shapes our bodies throughout our life. There is a particular need to understand what cancer looks like at its advanced stages, where treatments are often less likely to be successful. 

“The only way we can fully understand the impact of cancer across a lifetime, especially in the later stages of the disease when treatments often stop working, is by analysing tumour samples after people have died. People have selflessly agreed to take part in the PEACE study, knowing that they will not personally benefit from it.  

“I am in awe of people like Lydia who have taken part in the PEACE study. Faced with the life-changing news of a terminal cancer diagnosis, they have shown huge courage by deciding to help science after their death to benefit future generations of patients. Their legacy will be of saving the lives of others, and that is a truly humbling thought.”

Chief Investigator of the TRACERx study and Co-Chief Investigator of the PEACE study, Professor Charles Swanton (UCL Cancer Institute), added: “Many cancers can have poor survival because they have enormous potential to adapt and evolve and, by doing so, resist different forms of treatment towards the end of life. This research, alongside the TRACERx study, is revealing those patterns of evolution over the course of a lifetime.

“By understanding how cancer affects the body over the long-term, we can make better predictions about where it will go next and which treatments are likely to work best.” 

Dr Catherine Elliott, Director of Research at Cancer Research UK, said: “The TRACERx and PEACE studies are bringing exciting new insights into how cancer evolves over time. This fundamental understanding of cancer, particularly in its late stages, is essential if we are to offer better treatments for more advanced forms of the disease.

“This study relies on people making the brave and selfless choice in life to donate their body to support research after they die. We honour Lydia, and many other people who have donated samples to this study, for their commitment to a world where other people can live longer, better lives, free from the fear of cancer.”

The next phase of TRACERx, known as TRACERx EVO, will look in more detail at the processes underpinning metastasis to move towards better treatments for late-stage lung cancer. TRACERx EVO is currently underway and is backed by funding of £14.9 million from Cancer Research UK.

Patient’s story

Lydia Knott from Newtown Linford in Leicestershire volunteered to take part in both the TRACERx and PEACE studies after she was diagnosed with stage 4 lung cancer in 2014. Lydia had never smoked and drank very little alcohol, and the diagnosis came as a shock.

She initially had surgery, radiotherapy and chemotherapy to treat her lung cancer. Despite the best efforts of doctors, the cancer quickly spread to her brain and bones. Even so, thanks to previous research and developments in medicine, she continued her targeted cancer therapy medication and enjoyed a full and happy life for most of the next 10 years.  She died in April 2024 at the age of 87, at home, surrounded by her family. 

“Our mother was always super smart both in looks and intelligence” recalled her daughter Helen Knott. “On her return to the ward after major lung removal surgery, she was wearing lipstick. Apparently, the first thing she asked in recovery was whether any of the nurses had some she could borrow. Her zest for life was undiminished by illness.”

“She loved being around people.” added her son, Peter Knott. “She was always glamorously dressed and hosted lots of parties, with the family’s Boxing Day events a firm fixture in the village calendar for many years. Lydia was a pillar of the community in Newtown Linford, living there for over 70 years and serving as the village’s Parish Clerk for almost 50 years. 

“Our mother was a very optimistic and positive person who never stopped smiling despite her long illness. We are very proud of her selfless decision to agree to a research postmortem to collect samples for the PEACE study after her death, which means she leaves a legacy of improving cancer treatment for everyone.”

Links

• The paper in Nature
• Professor Mariam Jamal-Hanjani's academic profile
• Professor Charles Swanton's academic profile
• UCL Cancer Institute
• UCL Medical Sciences
• The Francis Crick Institute
• Cancer Research UK

Image

• Credit: Lung cancer cell dividing. Anne Weston, Francis Crick Institute. Source: Wellcome Collection.

Media contact

Tom Cramp

E: t.cramp@ucl.ac.uk