ANGLE plc, a world-leading liquid biopsy company, announced ground-breaking research by the world-class team at the Molecular Oncology Laboratory at the Swiss Federal Institute of Technology (ETH) Zurich, Switzerland. The study utilised the Parsortix® system to investigate the impact of sleep on the release of CTCs in preclinical models and 30 patients with breast cancer (21 with early stage and 9 with metastatic disease).
The Parsortix system provided biomarker-independent isolation and harvest of CTCs, CTC clusters and CTC-white blood cell (WBC) clusters. This was crucial in enabling the researchers to develop a new understanding of cancer metastasis with the discovery that the release of CTCs, CTC clusters and CTC-WBC clusters is highly dependent on the circadian rhythm with far greater metastatic activity during the rest phase (i.e. during the night). Not only are more CTCs, CTC clusters and CTC-WBC clusters released during the rest phase, but gene expression analysis (RNA sequencing) found that genes relating to cell division and metastatic potential were consistently upregulated, leading to more aggressive cancer cells.
These findings provide novel insight into the role of the circadian rhythm in the generation of CTCs with metastatic potential. This research could allow for the optimisation of cancer care by utilising time-controlled approaches for the treatment of breast cancer. For example, treatments which are most effective during the rest-phase, or which can reduce the impact of the circadian rhythm on CTC and CTC cluster release during the rest phase.
The research also identified the role of key circadian rhythm hormones in metastasis including melatonin, testosterone and glucocorticoids, which may provide targets for novel drug therapies and are likely to be of interest for investigation by biopharma companies.
Breast cancer is the leading cause of cancer in women. In 2022, it is estimated that c.290,000 women will be diagnosed with breast cancer and further c.3.8 million women are living with or after breast cancer in the US. Globally, the number of new breast cancer cases diagnosed each year is expected to increase by more than a third, and the number of deaths each year is expected to increase by more than 50% by 2040.
Professor Nicola Aceto, ETH Zurich, commented: “We have worked with the Parsortix system for over four years now. The ability to reliably harvest CTCs, CTC clusters and CTC-WBC clusters has allowed us to develop an understanding of cancer metastasis not previously possible. In this study we observed a striking and unexpected pattern of CTC generation dynamics in both patients with breast cancer and preclinical models, highlighting that most spontaneous CTC intravasation events occur during sleep.
Further, we demonstrate that rest-phase CTCs are highly prone to metastasize, whereas CTCs generated during the active phase are devoid of metastatic ability. These findings suggest the need for time-controlled approaches for the characterisation and treatment of breast cancer and the investigation of new drug targets.”
ANGLE Founder and Chief Executive, Andrew Newland, added: “We are delighted to report on this ground-breaking research which furthers the understanding of the metastatic process. Metastasis is responsible for 90% of cancer patient deaths so these findings mark a significant development in the understanding of cancer progression and provide novel insight for drug discovery. This study highlights the capabilities of the Parsortix system to harvest CTC clusters and CTC-WBC clusters, which are key to understanding the tumour microenvironment and immune system interaction and evasion. Pharma companies in discussion with ANGLE are showing increasing interest in investigating not only CTCs but also the associated immune cells (WBC) particularly when both cell types are found in the same cluster.”