Stopping cancer before it develops
Fresh insights into how cells alert the body when they are in danger of becoming cancerous could open new doors in the search for cancer therapies.
The body’s cells can sense when they’re about to become cancerous, and they can alert the immune system when they’ve become so damaged that they should be removed from the body. But could it be possible to fend off cancer altogether by capitalising on this process and improving it to ensure all precancerous cells are flushed from the body before they can cause harm?
Scientists at the University of Edinburgh have discovered that two key immune molecules could make that possibility a reality. They’re called toll-like receptors (TLRs) 2 and 10 and they can detect when cancer-causing genes, or oncogenes, have become active. This initiates a cascade of chemical signals that cause inflammation and trigger immune cells to remove the damaged cell. This process is called cellular senescence, and it prevents damaged cells from growing uncontrollably.
What is cellular senescence?
Cellular senescence is an anti-cancer mechanism characterised by a robust cell cycle arrest and the induction of a pro-inflammatory response. It limits the replicative capacity of cells, thus preventing the proliferation of cells that are at different stages of malignancy. Evidence suggests that induction of senescence can be exploited as a basis for cancer therapy. On the other hand, accumulation of senescent cells in the body contributes to the acceleration of ageing and age-related diseases, and elimination of senescent cells or attenuation of senescence-associated pro-inflammatory response through senotherapies (therapeutic strategies specifically targeting cellular senescence) has been proven effective in combating age-related pathologies.
Dr Juan-Carlos Acosta is a Cancer Research UK Career Development Fellow at the University, and part of the team that has published their observations in the journal Science Advances. He believes that interfering with TLR2/10 signalling could be a strategy for helping the body to clear pre-cancerous cells. The cells rely on the signals to become inflamed and set off on the road to becoming cancerous, making the two TLRs ideal drug targets.
Dr Acosta says: "The results of the study extend our knowledge of molecular mechanisms controlling senescence and may lead to new strategies for development of anti-cancer and anti-aging therapeutics based on innate-immune receptor manipulation.
"Damaged cancer-causing cells become senescent and are then killed by the body's own immune system. However, if the immune system does not destroy the senescent cell, the surrounding tissue can become inflamed, promoting cancer development.”
It is already known that TLR2 and TLR10 are able to detect viruses and bacteria but this is the first time they have been found to play a key role in cellular senescence. By discovering their role in cancer detection, the University’s team of scientists have provided a key insight into the molecular mechanisms that control senescence, which could lead to new strategies for fighting cancer.
Dr Acosta believes the research is vital because senescence has the potential to stop cancer development in the earliest stages.
“These findings show for the first time that damaged cancer-causing cells use TLR2/10 signalling to become inflamed, presenting potential drug targets that could help the body clear senescent cells before they cause harm.”
The new findings come just months after University researchers showed how the harm caused by senescence could be controlled or even stopped.
Scientists focused on a chain of harmful processes triggered by senescence, known as the senescence-associated secretory phenotype - a cascade of chemical signals that can promote damage to cells through inflammation.
The researchers showed that manipulating a cell's nuclear pores - gateways through which molecules enter the heart of the cell -- prevented triggering of the SASP, and also showed that DNA had to be reorganised in space within in the cell's nucleus in order for the SASP to be triggered.
“Our research really is fundamental to understanding how the body’s cells respond to damage and stress,” says Dr Acosta. “Although we are some way from being able to halt cancer and age-related diseases in their tracks, our work suggests ways in which scientists of the future might target these harmful effects.”