The Institute of Cancer Research, London, strongly welcomes the news that the targeted drug capivasertib, has been approved by the US Food and Drug Administration (FDA) for treating a type of advanced prostate cancer.
The decision provides the first regulatory seal of approval in prostate cancer and means that patients with PTEN-deficient advanced prostate cancer will be able to access the drug in the US.
The US approval has raised hopes that the medicine could also be approved for use in Europe and the UK. A regulatory application for the use of capivasertib in this setting is currently under review in the EU.
Burden of advanced prostate cancer
Prostate cancer is the second most common cancer in men and the fifth leading cause of male cancer death globally, with more than 1.4 million people diagnosed each year.
Of these, approximately 200,000 patients worldwide, including 35,000 in the US, are diagnosed with advanced prostate cancer annually. About a quarter of these patients have PTEN-deficient tumours, an aggressive form of the disease associated with poor outcomes.
Capivasertib is a first-in-class drug that works in a new way, by blocking the activity of the cancer-driving protein molecule AKT, which when activated transmits signals through the PI3 kinase pathway to drive cancer cell growth.
Targeting the AKT pathway
Capivasertib was discovered by AstraZeneca subsequent to a collaboration with Astex Pharmaceuticals and its collaboration with The Institute of Cancer Research (ICR) and Cancer Research Technology Limited.
The FDA’s decision was based on results from the international phase III CAPItello-281 trial which showed that adding capivasertib to standard treatment delayed the growth or spread of cancer. The standard treatment involved the use of abiraterone, previously discovered at ICR.
Patients who received the combination treatment of capivasertib plus abiraterone lived a median of 33.2 months before their cancer worsened, compared with 25.7 months for those on standard treatment with abiraterone alone — a difference of 7.5 months.
Early results also suggest the treatment may help patients live longer overall, but further follow-up is needed to confirm this.
Years of fundamental research
The success of capivasertib followed years of fundamental research at the ICR, aimed at understanding how the AKT protein molecule is regulated, aimed at understanding how the AKT protein molecule is regulated. In 2002, ICR scientists published the 3D structure of AKT and showed how the protein is activated – explaining how AKT exerts its cancer-driving behaviour and providing the basis for the creation of a drug informed by the structure.
Researchers in the ICR’s Centre for Cancer Drug Discovery, with funding from Cancer Research UK, established a drug discovery project and then worked in collaboration with Astex Pharmaceuticals to design small-molecule inhibitors which would target AKT, based on its 3D structure.
Fragment-based drug design approach
They used a technology called ‘fragment-based design’ where tiny fragments were initially found that attach weakly to the AKT protein, and then these were extended to produce a tighter fit and potent inhibition of AKT’s cancer-driving behaviour.
In 2005, a series of prototype drug compounds discovered by the ICR and Astex was shown to have very promising activity against a range of human tumours grown in mice and was licensed to AstraZeneca. Then, in 2010, AstraZeneca announced its discovery of capivasertib and began to develop the drug as a potential treatment for various forms of cancer.
Earlier success in breast cancer
Following results from the international phase III CAPItello-291 trial which showed that capivasertib doubled the time it took for cancer to progress in people with advanced ER positive, HER-2 negative breast cancer with PI3 kinase pathway mutations, FDA approval was granted in 2023.Earlier success in breast cancer
In April 2025, NICE recommended capivasertib, in combination with fulvestrant, for patients in England and Wales with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER-2) negative breast cancer, with PIK3CA, AKT1, or PTEN mutations whose disease has advanced or spread following treatment.
ICR researchers have explored the use of AKT inhibitors such as capivasertib in prostate cancer, including a study published in Nature Communications in 2025 showing that combining AKT inhibition with other targeted treatments could kill cancer cells and slow tumour growth in models of advanced disease.
‘An important step forward’
Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said:
“This approval marks an important step forward for patients with advanced prostate cancer, particularly those with PTEN deficient disease who urgently need more targeted treatment options.
“Capivasertib is the result of decades of research into how cancer cells grow and survive, and it is encouraging to see these scientific advances translating into new treatments for patients.
“While further follow-up is needed to confirm the full benefit for survival, these results show the real potential of targeting the AKT pathway to improve outcomes for people with this aggressive form of prostate cancer.”
From early discovery to patient benefit
Professor Paul Workman OBE, Harrap Professor of Pharmacology and Therapeutics at The Institute of Cancer Research, London, former ICR CEO and Director of the Centre for Cancer Drug Discovery and an active researcher on the AKT drug discovery project, said:
“This approval is a powerful example of how fundamental discovery science can lead to new treatment approaches for patients.
“Research at the ICR helped understand the activity of AKT as a key driver of cancer and our elucidation of its 3D structure guided efforts to design drugs to block it. These early discoveries, together with collaboration with our partner Astex Pharmaceuticals, laid the foundations for the subsequent development of capivasertib. In particular, we used fragment-based design to create advanced prototype drugs that showed clear proof-of-concept activity in human tumour xenograft models – including one where the PI3 kinase pathway was activated by PTEN deficiency.
“It is very rewarding to see our ICR science now contributing to a new treatment option to help patients with advanced prostate cancer, building on capivasertib’s earlier success in treating breast cancer.”