Researchers from the Institute of Cancer Research (ICR) have used MR elastography to visualize and measure the stiffness and density of tumour tissues in mice. The non-invasive imaging technique provides crucial new information about cancer architecture and could help deliver treatment to challenging tumours (Cancer Research 10.1158/0008-5472.CAN-19-1595).
Tumours are formed from dense and compact networks of cells, structural fibres and blood vessels. Some tumour types are particularly stiff and dense, which makes it difficult to deliver drugs deep inside the tumour mass and hinders treatment. Tissue stiffening is also associated with tumour progression and metastasis. The major contributor to this increased stiffness is collagen – a key component of bone, cartilage, tendons and the extracellular matrix that holds tissues together.
Drugs designed to break down the extracellular matrix, such as collagenase, can weaken the structure that holds a tumour together and allow other cancer drugs to reach cells in its centre. Assessing the contribution of collagen to relative stiffness could identify tumours with the potential to be treated by with such drugs.
The ICR researchers, working in collaboration with King’s College London, combined MR elastography with computational histopathology to investigate the contribution of collagen to the biomechanics of several different tumour types in mice. They found, for example, that breast tumours were around twice as stiff as brain tumours and around three times as dense.
The pre-clinical study demonstrated that increased collagen correlated with elevated tumour elasticity and viscosity, with collagen key to keeping breast and pancreatic cancers stiff and inaccessible to treatments. In contrast, tumours arising from the nervous system, such as some forms of childhood cancer and brain tumours, were relatively soft and lacking in collagen.
“Our research shows that this new type of scan can give valuable diagnostic information about breast and pancreatic tumours non-invasively by assessing their stiffness,” explains study co-leader Simon Robinson. “If confirmed in a clinical trial, we could use this technique to identify patients most likely to benefit from treatments that target the dense scaffold upon which these tumours grow.”
The researchers also used MR elastography to monitor the weakening of tumour structure following treatment with collagenase. They found that collagenase resulted in a clear reduction in the elasticity and viscosity of breast tumours in mice – both of which fell by around a fifth. This finding suggests that the technique, which can be performed on a conventional clinical MRI scanner, could help identify the optimum time at which to deliver chemotherapeutic drugs by showing when the tumour is most vulnerable.
“There’s a lot of research activity centred on finding new therapies designed to help anti-cancer drugs reach their target in breast and pancreatic cancers, which can be so stiff and dense that they are impenetrable,” says study co-leader Yann Jamin. “We are very excited to have found a rapid scan that can be incorporated into a current routine clinical MRI examination and can potentially monitor the effects of these new tumour-weakening therapies, and assist the development and delivery of medicines which could save or extend lives.”
