A new weapon in the fight against cancer

Cancer happens when cells in the body start growing uncontrollably. But what if the tissue surrounding a tumour could be enlisted to stop the cancer spreading? New research gives the first evidence of how this might be possible by treating mice with a new drug that made cancer cells less likely to grow in other parts of the body.

Many cancer researchers believe that targeting the spread of cancer to other organs, otherwise known as metastasis, holds the key to successfully treating the disease because metastasis is the cause of death for 90% of those who die of cancer.

In the past, many treatments aimed at preventing metastasis have been targeted at tumour cells themselves, for example with chemotherapy, which can have severe side effects. This approach can show some success but after a while the tumour cells can become resistant to the treatment and the cancer then spreads.

Welcome environment

Recent research has also shown that the cells and proteins that surround a tumour play an important role in determining how it behaves. As a tumour develops, it sends out messages to surrounding cells, recruiting their help in creating a micro-environment with suitable conditions for the cancer to spread. These cells can then communicate with the tumour cells to encourage them to grow.

A large proportion of the cells found in the tumour micro-environment are cancer-associated fibroblasts (CAFs). In normal tissue, fibroblasts help to build the protein scaffolding or “matrix” that gives our organs their shape and helps heal wounds. However in cancer, fibroblasts are co-opted into re-sculpting and stiffening the surrounding matrix. This helps the tumour to grow larger by encouraging cells to divide and allows cancer cells to escape into the bloodstream from where they can then spread to other parts of the body.

The new study, by researchers at the Francis Crick Institute and published in EMBO Reports, found that when CAFs were grown in low-oxygen conditions they no longer attempted to change the structure of the surrounding scaffolding and started behaving more like normal fibroblasts again. The matrix remained flexible and, crucially, tumour cells were then unable to spread through it. The research provides the first clues of how we could target this process and help bring the cancer-associated fibroblast cells back on side against the cancer.

Further experiments found that the CAFs’ change in behaviour was caused by a protein that is involved in sensing the amount of oxygen available to the cells. The team then used a drug in the mice with cancer that fools this oxygen sensor into behaving as if there is no oxygen present. They found that the cancer was then less likely to spread in those mice that had been treated with the drug than in those that hadn’t.

Promising approach

As the team involved in the study readily acknowledge, this approach is still very much in its infancy. However, it is an exciting development in the way we think about how cancer can be treated. One of the great challenges in cancer treatment is that tumour cells are genetically unstable and as a result can become resistant to chemotherapy. CAFs and other cells are more stable and so will hopefully be less likely to develop resistance to emerging treatments if the findings of the research fulfil their promise.

As our understanding of the complex relationship between cancer and our bodies evolves, we will find new ways to target and combat the disease. It is very likely that the chemotherapies of the future will exploit these interactions, providing hope for better, more effective treatments.

This article is published in collaboration with The Conversation. Read the original article.. Publication does not imply endorsement of views by the World Economic Forum.

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Author: Sarah Allinson, Senior Lecturer, Lancaster University.

Image: A radiologist examines the brain X-rays of a patient who underwent a cancer prevention medical check-up at the North Bengal Oncology Center, a cancer hospital, on the outskirts of the eastern Indian city of Siliguri. REUTERS/Rupak De Chowdhuri