Drug that targets ‘on switch’ in cancer cells moves one step closer

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A new targeted therapy that could combat drug resistance has been found to be safe in early trials, allowing it to move to the next stage of development.

Research published in the journal Clinical Cancer Research also gave early indications that the drug, called AZD5363, can shrink tumours in some patients with a specific ‘on switch’ in their tumours.

The drug was discovered by AstraZeneca, following on from research by teams at The Institute of Cancer Research, London – partly funded by Cancer Research UK – and Astex Therapeutics.

Tested for safety and dosage

In a new study – led by Dr Udai Banerji, Deputy Director of the Drug Development Unit at the ICR and The Royal Marsden NHS Foundation Trust – the researchers explain how they tested AZD5363 in 90 patients with a variety of cancer types, treated at a range of centres across Europe and North America.

The drug blocks a molecule called AKT, which plays a key role in a mechanism that cancer cells rely on to survive, grow and resist treatment.

Using a range of doses, the team was able to collect data on which side effects the patients reported, and combine this with the results of tests that showed how the drug interacts with the body.

Their aim was to determine whether AZD5363 was safe, and what dose it should be given at in future trials.

Crucially, the researchers found that the drug was safe at levels that are known to shrink tumours in mice.

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Promising approach

Following the tests for safety and dosage, the research team tested AZD5363 in 54 women with breast, ovarian, cervical or uterine cancer who had faults in a gene called PIK3CA.

PIK3CA helps to activate AKT, and mutations in the gene are often found in breast and gynaecological cancers.

Around half of the women showed a small decrease in tumour size, giving the researchers early clues that targeting AKT is a promising approach in women with PIK3CA mutations.

The researchers also studied blood, hair and tumour samples from the patients, and found evidence that the drug was able to block AKT.

Based on these results, the team has started work on further international trials led by AstraZeneca and the ICR. These trials will combine AZD5363 with chemotherapy and hormonal therapy in breast and prostate cancer.

Studies on combination treatment underway

Dr Udai Banerji, Deputy Director of the Drug Development Unit at the ICR and The Royal Marsden, said:

“Cancers are often dependent upon rogue genes that, when switched on, make them grow uncontrollably and make them resistant to existing treatment. It is exciting to have drugs that can switch off these genes in our clinics.

“Our study found that this new drug, AZD5363, could effectively knock out a key mechanism that cancer cells use to become drug resistant. Studies are now under way to test whether the treatment could be effective in combination with other therapies for patients with breast and prostate cancers.”