Cancer therapies that cut off blood supply to a tumour could more effectively treat the deadly disease when combined with existing chemotherapeutic drugs, a study has found. The research, published in the journal EMBO Reports, showed that tumour growth is better-reduced in mice when the expression of a particular protein called Beta3-integrin is targeted in combination with drugs that are already used in cancer patients. The findings could help fine-tune treatment for cancer patients and revitalise an interest in the use of microtubule targeting agents (MTAs) which are commonly used as chemotherapies in cancer patients.
“Tumours must recruit their own blood supply to grow beyond a very small size and this process is called angiogenesis,” said Stephen Robinson from the University of East Anglia in the UK. “Anti-angiogenic drugs stop tumours from growing their own blood vessels, and this in turn can slow the growth of the cancer, or shrink it. Targeting angiogenesis is therefore seen as crucial in many anti-cancer strategies,” said Robinson.
“However many anti-angiogenetic therapies target proteins that help the functioning of a patient’s normal blood supply – and this can lead to nasty side effects including haemorrhage, strokes, high blood pressure, and fatigue,” he said. Researchers have long looked at Beta3-integrin as a better anti-angiogenic target because the protein is not expressed in normal blood vessels, but is expressed in tumour blood vessels.
This reduces the potential for unwanted side effects. Targeting Beta3-integrin in combination with microtubule targeting agents, which are widely used in cancer patients, works better than targeting Beta3-integrin alone, researchers said. Microtubules are protein structures in cells that help them move and divide.
Specifically, researchers looked at how Beta3-integrin and microtubules interact with one another in the cells that line blood vessels (endothelial cells), and showed that microtubules behave differently when Beta3-integrin levels are reduced; the microtubules become more sensitive to the chemotherapies that are used to hit them.
“This protein, Beta3-integrin, has been the focus of drug design over the last two decades because its expression is vastly increased in endothelial cells during blood vessel recruitment to tumours,” Robinson said. “We found that targeting the protein Beta3-integrin in combination with the use of microtubule targeting agents (MTAs) could be a good way to stop tumours recruiting a blood supply to grow,” he said.
“This is really important because MTAs are already in clinic and commonly used as chemotherapies such as paclitaxel in cancer patients. Meanwhile Beta3-integrin inhibitors have been at the centre of cancer drug design for over 20 years and are well-tolerated in clinical trials,” he added.