A study to learn more about non small cell lung cancer (TRACERx)

Study design
This study was for people with non small cell lung cancer (NSCLC) that had not spread beyond one side of their chest. They were all due to have surgery to remove their lung cancer.

The research team took regular blood samples and a sample of the cancer that was removed during the operation. They also took another sample of cancer cells from people later on if their cancer had spread, when this was possible.

Results
Some groups of researchers have started to publish results for TRACERx. The results we know about so far are summarised below. We plan to update this page as more results are available. 

There are links to more detailed information at the bottom of this page.

Genetic changes in cancer cells
In April 2023, the trial team published results looking at the genetic material (DNA) inside cancer cells. This included analysing genes in different areas of the same tumour.

They looked at hundreds of cell samples. Some people had lung cancer that had spread to another part of the body. Some people had lung cancer that had not spread. The research team compared the results to find out more about what makes certain cancers more likely to spread.

Their main findings were that:

• different areas of the same cancer have different genetic changes
• it is important to take lots of samples to make sure you find the different genetic changes
• looking at different genetic changes can help predict whether a cancer is likely to spread or not
• there are different cells within tumours, and cancers are more likely to spread from cells that grow across a larger area of the tumour
• when people have genetic material from cancer cells in their blood (circulating tumour DNA , or ctDNA), the cancer is more likely to spread
• viral genetic material we inherited from ancestors thousands of years ago may affect how quickly cancer grows

They were able to gather a lot of information about genetic changes in cancer cells. They hope this will help researchers in the future find out more.

Extreme weight loss (cachexia)
In April 2023, they also published results about why some people develop cachexia. This is when people lose a large amount of weight, muscle mass and body fat. People who have cachexia often don’t live as long.

The team found several changes in genes, proteins and immune system cells that could be linked to cachexia. In particular, people with high levels of a protein called GDF15 in their blood are at increased risk of cachexia. The team hope they can use this research to help manage cachexia in people with cancer in the future.

Air pollution
In October 2022, the researchers presented some results about the effect of air pollution on lung cells. They wanted to find out more about causes of lung cancer in people who have never smoked. 

It is common for people with non small cell lung cancer (NSCLC) who have never smoked to have changes (mutations) in a gene called EGFR.

In this analysis, they looked at the link between NSCLC with EGFR changes and tiny (microscopic) particles in the air. These are called particulate matter, or PM. They can include particles such as smoke, soot and dust.

The team looked at thousands of people and analysed hundreds of tissue samples. They found that an increased exposure to particulate matter can change the way the immune system works. And that this can increase the risk of NSCLC developing. This is for people with a change in the EGFR gene.

PM can also increase the risk of other cancers including:

• other types of lung cancer  
• mesothelioma
• some bowel cancers
• some head and neck cancers

They concluded that particulate matter can increase the risk of some cancers. And that this is evidence for limiting air pollution.

Artificial intelligence
In May 2020, a group of researchers published results about a computer programme or artificial intelligence (AI) tool. The aim of the tool was to find out which people have a higher chance of their lung cancer coming back. 

Computer scientists and specialist doctors called pathologists trained the AI tool to pick out cancer cells and immune cells in tissue samples.

The tool helped them see that different areas of cancer had different numbers of immune cells. They think this means that some areas of the cancer can hide from the immune system. 

When they looked in more detail, they found that cancer with fewer immune cells is more likely to start growing again. They hope that in future doctors can use an AI tool to help them decide which treatment is best.

Circulating tumour cells
In 2019, researchers looked at circulating tumour cells (CTCs) in 100 people who were due to have surgery for lung cancer. CTCs are tumour cells that have broken away from the lung cancer and are circulating in the blood. 

They found the cancer was more likely to come back in people who had more CTCs in their blood when they had their operation. 

ORACLE test
In October 2019, another group of researchers developed a test called ORACLE. It helped identify people who had a high risk that their cancer would come back. They hope in the future doctors can use it to help decide which treatment people should have.

Immune system cells
Also in October 2019, another research group looked at immune system cells called lung T cells. They found a unique set of T cells that could recognise and fight the cancer. They found the same T cells in blood samples taken when people had surgery to remove the cancer. 

The researchers hope they can use this to develop a blood test to show how well treatment is working. Or possibly to develop treatment using specific T cells.

More detailed information

Please note - the information we link to here is not in plain English. The articles have been written for health care professionals and researchers.

The evolution of lung cancer and impact of subclonal selection in TRACERx (genetic changes)
A Frankell and others
Nature, 2023. Volume 616, pages 525 - 533.

The evolution of non-small cell lung cancer metastases in TRACERx (cell changes)
M Al Bakir and others
Nature, 2023. Volume 616, pages 534 - 542.

Genomic-transcriptomic evolution in lung cancer and metastasis (genetic changes)
C Martinez-Ruiz and others
Nature, 2023. Volume 616, pages 543 - 552.

Antibodies against endogenous retroviruses promote lung cancer immunotherapy (immune system changes)
K Ng and others
Nature, 2023. Volume 616, pages 563 - 573.

Evolutionary characterization of lung adenocarcinoma morphology in TRACERx (cell changes)
T Karasaki and others
Nature Medicine, 2023. Volume 29, pages 833 - 845.

Body composition and lung cancer-associated cachexia in TRACERx (cachexia)
O Al-Sawaf and others
Nature Medicine, 2023. Volume 29, pages 846 - 858.

Mechanism of action and an actionable inflammatory axis for air pollution induced non-small cell lung cancer: Towards molecular cancer prevention (air pollution) 
C Swanton and others
Annals of Oncology, 2022. Volume 33, supplement 7, page S1413 (abstract LBA1)

Geospatial immune variability illuminates differential evolution of lung adenocarcinoma (artificial intelligence)
Khalid AbdulJabbar and others
Nature Medicine, 2020. Issue 26, volume 7, pages 1054 - 1062.

Pulmonary venous circulating tumor cell dissemination before tumor resection and disease relapse (circulating tumour cells)
F Chemi and others
Nature Medicine, 2019. Volume 25, issue 10, pages 1534 -1539.

A clonal expression biomarker associates with lung cancer mortality (ORACLE test)
D Biswas and others
Nature Medicine, 2019. Volume 25, issue 10, pages 1540 - 1548.

Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer (immune system cells)
K Joshi and others
Nature Medicine, 2019. Volume 25, pages1549–1559.

Where this information comes from    
We have based this summary on the information in the articles above. They have been reviewed by independent specialists (peer reviewed ) and published in medical journals. We have not analysed the data ourselves.