Using molecular clocks to tell cancer time

We all know tracking metastatic cancer progression is vital for ongoing monitoring of cancer patients, but how do metastatic cancers arise in the first place? Are they seeded simultaneously throughout the body, or do they arise progressively? How are they related to the original tumour? More importantly, how do different metastases respond to treatment, and how can we track this? Amazingly, new insights from the UK’s LEGACY breast cancer program is shedding light on some of these important questions! 

This study simultaneously examined biopsies of primary and secondary tumours from two breast cancer donors, which revealed that secondary tumours were predominantly seeded from a single cell lineage of the primary tumour. This indicates a remarkable phenomenon of monoclonal seeding for metastatic breast cancers, which also aligns with previous studies showing the same progression in colorectal cancers. 

The good news is that if cancer metastases are clonal, the ability to track their dissemination and dynamics becomes more plausible. As a first step to prove this, scientists in this study used chemical markers that progressively accumulate in DNA, serving as molecular clocks to lineage trace metastatic cancers as they spread to secondary sites. These markers can be used for metastatic cancer monitoring by charting secondary cancer ‘family trees’ for each patient. 

Next, they leveraged an easily available resource: circulating tumour DNA in blood samples from breast cancer patients. The specific molecular clock markers found in tissue samples from primary or secondary tumour biopsies were found to correlate highly with their frequency of occurrence in plasma tumour DNA. 

This is very encouraging, as it opens up a range of possibilities for following cancer progression using regular blood tests. First, metastases formation can be closely monitored, and their evolutionary lineages can be traced to the original tumour using these molecular clocks, which could point to initial treatment options. Secondly, relative pathogenic impacts of secondary tumours can also be assessed by monitoring levels of their lineage-specific molecular markers in the blood. Finally, the responses of the various metastatic tumours to different therapies can be tracked, providing the doctors with valuable real-time information that can be effectively used to optimise personalised medical treatment for each patient.

We are very excited by ongoing genomics research to develop new ways of monitoring cancer evolution, pathogenicity, and treatment outcomes using the relatively simple process of blood biopsies which will deliver better options for patients. SeqOne will continue to closely monitor progress in this rapidly growing field to enable seamless incorporation of these new techniques into our software platform for enhanced clinical outcomes.

Original article: https://www.nature.com/articles/s41467-020-15047-9