Cancer therapies are designed to kill tumour cells, but produce tumour cell debris in the process.
In a study published in The Journal of Experimental Medicine, researchers from Brigham and Women’s Hospital and colleagues show that leftover debris can stimulate inflammation and tumour growth, but that molecules called resolvins can block that unwanted inflammatory response.
The findings point towards a new way to enhance the effectiveness of current cancer therapies and potentially prevent tumour recurrence.
When conventional cancer treatments, such as radiation or chemotherapy drugs, break apart tumours, they can also spread and stimulate the production of proinflammatory cytokines.
These signalling molecules, known to promote tumour growth, were at the centre of the investigation.
“Dead and dying tumour cells are an under-appreciated component of the tumour microenvironment that may promote tumour progression,” said Professor Charles Serhan, PhD, DSc, Department of Anesthesiology, Perioperative and Pain Medicine at BWH.
The team administered a variety of therapeutic drugs to lab-cultured cancer cells and collected the resulting debris.
When co-injected into mice with a small number of non-growing cancer cells, the debris stimulated tumour formation.
A similar test treated mice with the chemotherapy drugs such as cisplatin and vincristine to generate debris in vivo, supporting the conclusion that the debris helped surviving cancer cells form tumours.
The researchers concluded that a lipid called phosphatidylserine stimulated immune cells to produce a “cytokine storm” when exposed to the cancerous cells and caused the growth.
The researchers reasoned that if drug-generated debris was promoting tumour growth, clearing the debris might stop it.
The team focused on the body’s own resolvins which act as stop signals to end or “resolve” the inflammation.
Resolvins counter the debris-stimulated proinflammatory cytokines and stimulate the immune system including white blood cells called macrophages (“the big eaters”) to remove or “mop up” the debris.
Resolvins are biosynthesised by the body from omega-3 essential fatty acids.
Resolvins were discovered at the Brigham and Women’s Hospital by Dr. Serhan and his laboratory and are a new approach to turn off inflammation in the human body to prevent a “cytokine storm” rather than blocking a single pro-inflammatory factor
Treating mice with small amounts of resolvins inhibited the subsequent therapy-stimulated tumour growth and prevented cancer cells from spreading.
Resolvin treatment enhanced the activity of several cytotoxic therapies against a variety of tumour types resulting in tumour regression.
Clinical developments using resolvins as potential therapeutic approaches are already in progress for several inflammatory and neurodegenerative diseases.
“Stimulating the clearance of tumour cell debris via specialised pro-resolving mediators represents a new approach to prevent tumour growth and recurrence,” the authors write.
Source: Brigham and Women’s Hospital