Primary tumours can pre-programme cancer cells to become dormant once they have spread around the body, helping them survive cancer treatment.
The discovery was made by a team of researchers at Mount Sinai Hospital whilst studying the relationship between cancer therapy resistance and an environmental state found in tumours called hypoxia.
Prior to this study, hypoxia – an oxygen-deficient environment – was understood to be a ‘hallmark’ of cancer that induces stress responses, dormancy and therapy resistance. However, scientists had never established exactly how it helps cancer cells that have spread around the body to survive.
Researchers created hypoxic and non-hypoxic environments within head and neck and breast tumours by implanting drugs that could induce hypoxia. By creating these microenvironments in live tumours, researchers could isolate cancer cells as they moved from the primary tumour to the lungs in mouse models.
The team found that those isolated cells derived from hypoxic areas of the primary tumour were able to grow into metastases and were more likely to go into a state of dormancy, compared to cells from non-hypoxic areas of the tumour.
The results suggest that hypoxia could not only induce the activation of characteristics related to more aggressive cancers, but also create dormant cancer cells that could evade modern-day cancer therapies.
In addition, investigation of the genetics of both primary tumour cells and metastatic cells indicated certain correlations between activated genes, suggesting there could be scope to create a marker test to predict therapy resistance in patients.
“This research highlights the signals in the primary tumour that instruct disseminated cancer cells to become dormant,” said Julio Aguirre-Ghiso, the study’s senior investigator. “Dormant cells must be targeted to address the whole spectrum of the disease and attacking the cancer.”
The findings could help develop new cancer treatments capable of treating metastatic disease and treatment resistance – two aspects of cancer that greatly increase the chances of death from the disease.
“Recurrence of cancer after initial treatment remains a critical unsolved problem for too many patients,”said William Oh, professor of Clinical Cancer Therapeutics at The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai. “This highly innovative research provides a novel path forward for targeting dormant cancer cells which may be ‘hiding’ from our available therapies and which may need additional drugs to root them out and improve cure rates.”