Drug may boost radiotherapy effect on several cancers

1 Jun

Some tumors grow so fast that their cells become oxygen-starved from inability to hook up to the body’s

blood supply. Oxygen-starvation usually triggers signals that cause cell suicide, but in some cancers with a

faulty p53 tumor suppressor gene – which is found in around half of cancers – the cells carry on growing because

the cell-suicide signals fails.

radiotherapy machine
Drugs already being trialed could boost the effectiveness of radiotherapy treatment for many types of cancer.

Now, researchers have discovered that giving a class of drugs called AKT inhibitors in combination with

radiotherapy may boost the effectiveness of the treatment on tumors with the faulty p53 gene by restoring cell

suicide in oxygen-starved cancer cells and making them more radiation-sensitive.

The team – from Cancer Research UK – reports the findings in the Journal of Clinical


Dr. Ester Hammond, study leader and Cancer Research UK scientist based at the University of Oxford, says:

“This exciting discovery sheds light on the role of oxygen-starvation in cancer development and

suggests that drugs already being trialed in cancer patients could potentially boost the effectiveness of

radiotherapy across a range of cancers.”

In their study, Dr. Hammond and colleagues found that six genes that normally protect the body against cancer

are less active in oxygen-starved cancer cells with a faulty p53 gene.

They found the six genes from analyzing lab-grown cancer cells, and then showed they were also affected by

p53 in a range of human cancers, including breast, brain, colorectal, kidney, bladder and melanoma cancers.

Active AKT prevents cell suicide even under oxygen-starvation

The team also found that when two of the genes are inactivated – PHLDA3 and INPP5D – another gene called AKT

becomes permanently switched on, which prevents cell suicide, even though the cancer cells are oxygen-starved.

They then tested the effect of AKT inhibitors in lab-grown cancer cells and mice lacking the p53

gene when treated with radiotherapy. The results showed the radiotherapy killed more tumor cells.

The researchers conclude that their results identify a number of factors that influence cell suicide via the

p53 gene, and suggest “AKT inhibition may improve radiotherapy response in p53-deficient tumors.” Dr. Hammond


“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


As more than half of cancer patients receive radiotherapy as part of their treatment, says Eleanor Barrie, senior

science information manager for Cancer Research UK, anything that improves the effectiveness of

radiotherapy is “great news for patients.”

In their discussion of the results, the researchers suggest it is likely that under oxygen-starvation, p53

also has other anticancer roles, other than driving cells to commit suicide, and note it “would be interesting

to investigate” whether any of the targets they identified in their study affect other anticancer cell

functions under oxygen starvation.

Meanwhile, MNT recently reported how a form of permanent radiotherapy

may prolong prostate cancer survival. For that study, researchers compared low-dose-rate prostate

brachytherapy (LDR-PB), where seeds of radioactive material are implanted in the prostate – to dose-escalated

external beam radiotherapy (EBRT), where beams of radiation are focused on the prostate gland from outside the


Five years after treatment, they found that the men treated with LDR-PB were more than twice as likely to be

free of prostate cancer as those treated with DE-EBRT.