We find out about new research that uncovers how breast cancer cells survive and become resistant to treatment in low oxygen conditions.
In order to grow, breast cancer cells need nutrients and oxygen, which are provided by the surrounding blood vessels. However, as the tumour becomes larger it outgrows its blood supply, meaning that some cells are starved of oxygen. Rather than causing the cells to die, as you might expect, low levels of oxygen can actually lead to genetic changes in the cancer cell, which have been associated with resistance to treatment and cancer spread.
Working closely with Professor Adrian Harris, Dr McIntyre and his team have identified several ways to target cancer cells in order to prevent damaging genetic changes occurring in response to low oxygen levels. This may ultimately lead to more effective treatments and better outcomes for patients.
A new drug to tackle triple negative breast cancer?
Dr McIntyre has been investigating how triple negative breast cancer, which can be an aggressive form of the disease, is encouraged to grow and spread to other parts of the body when oxygen levels are low. A lack of oxygen in the tumour causes a protein called BET to switch on several genes that encourage the tumour to grow, such as VEGF-A which activates the growth of new blood vessels. In research published today, the team found that a drug known as JQ1 can prevent BET from switching on these genes, thus making it more difficult for the tumour cells to survive in low oxygen conditions.
Currently, a group of drugs that are very similar to JQ1 are being investigated in clinical trials for use in several different types of cancer. If these trials are successful, and with the added weight of Dr McIntyre’s lab findings, the researchers are hopeful that a clinical trial of JQ1 could begin within a few years to find out whether it can benefit triple negative breast cancer patients.
Bicarbonate - is blocking this molecule key to killing cancer cells?
The pH level of a cell measures how acidic or alkaline the environment is and must be tightly controlled - even small changes to pH can affect how the cell functions. Low oxygen levels cause the pH to become more acidic; in healthy cells this may be damaging and can even kill the cell, however tumour cells can adapt to the acidic conditions in order to survive.
One of the ways that cancer cells have adapted to low oxygen conditions and increased acidity is to activate an enzyme called CA9, which has been linked to tumour growth and cancer spread, leading to poorer outcomes for patients. CA9 has an important role in balancing pH; the enzyme produces an alkaline molecule called bicarbonate, which is transported into the cell to neutralise the increased acidity caused by the low oxygen conditions.
In recently published research, Dr McIntyre and his team have shown that by blocking the mechanisms that move the bicarbonate into the cell (known as transporter molecules), the growth of cancer cells can be reduced as they are no longer able to balance their pH levels.
In the future, it may be possible to target these transporter molecules with drugs in order to prevent cancer cells surviving in low oxygen conditions. Dr McIntyre believes these drugs, if given in combination with existing drugs that starve the tumour of oxygen, could provide a desperately needed alternative for the thousands of patients who develop resistance to today’s treatments.
Image: D Sharon Pruitt