Discovery could improve effectiveness of radiotherapy in a wide range of cancers

Administering AKT inhibitors in combination with radiotherapy might boost its effectiveness across a wide range of cancers, according to a study published in the Journal of Clinical Investigation (2015; doi:10.1172/JCI80402).

Tumors often grow so quickly that some of the cells do not have access to the body's blood supply, causing them to become oxygen-starved. This rapid growth usually sends signals to the cells to die, but in cancers with faults in the p53 gene, which is present in at least half of all cancers, this signal is blocked and so the cells continue growing.

In this study, the researchers found six genes that help protect the body against cancer were less active in oxygen-starved cancer cells when p53 was faulty.

In the absence of PHLDA3 and INPP5D genes, the AKT gene becomes permanently switched on, preventing the cells from dying despite being oxygen-starved.

When drugs designed to block AKT were given to mice with tumors and lab-grown cancer cells lacking p53, the radiotherapy killed more tumor cells.

Importantly, lower activity in these genes was also linked to poorer survival in patients with a variety of different cancers. This suggests that adding AKT inhibitors to radiotherapy could be an effective way to treat many cancers.

“This exciting discovery sheds light on the role of oxygen starvation in cancer development and suggests that drugs already in trials in cancer patients could potentially boost the effectiveness of radiotherapy across a range of cancers,” said study leader Ester Hammond, PhD, a Cancer Research UK scientist at the University of Oxford in the United Kingdom. “We hope that this important piece of the jigsaw will support ongoing efforts to develop drugs that enhance radiotherapy, so that even more patients can benefit from this cornerstone of cancer treatment.

“Advances in how we give radiotherapy and use it in combination with other treatments have the potential to improve survival for thousands of cancer patients. More than half of all cancer patients receive radiotherapy as part of their treatment, so anything that can be done to improve its effectiveness is potentially great news for patients,” said Eleanor Barrie, Cancer Research UK's senior science information manager.

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