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Scientists have identified a novel two-pronged treatment approach that offers significant promise for patients suffering from advanced disease. prostate cancer,
Experts at The Institute of Cancer Research, London, found that this approach could benefit up to 40 percent of people with end-stage disease.
This strategy uses existing cancer drugs, or drugs in development, to effectively slow tumor growth and induce cancer cell death. Researchers aim to combine drugs that attack the proteins that promote the survival of cancer cells.
The new combination was tested against cancer cells that had become resistant to hormone therapy, knowing that, among this patient group, outcomes worsen when they become resistant. Treatment,
MCL1 is a protein that promotes cancer cell survival and the protein AKT plays a key role in the mechanism that many cancer cells rely on to survive, grow, and resist treatment.
Research published in the journal Nature Communications found that inhibiting MCL1 and AKT at the same time led to prostate cancer cell death.
The scientists explained that in humans, drugs targeting MCL1 have had limited success in the past, so they planned to target the protein indirectly by inhibiting another protein that regulates MCL1 levels using the drug fadraciclib – a drug discovered by the ICR a few years ago that is currently in clinical trials for blood cancer.
The team either blocked AKT using a drug called ipatasertib, which is being investigated as a potential treatment for several different cancers, or used another drug called capivasertib — which is used to treat certain types of breast cancer.
In laboratory studies, they found that combining fadraciclib with capivasertib or ipatasertib led to prostate cancer cell death.
Specifically, they found that prostate cancer cells that had a certain type of tumor, which affects 40 percent of patients, known as PTEN-loss/PI3K-activated, responded best to the combinations.
Subsequent trials in mice with this tumor type showed that the combination significantly slowed cancer growth, according to the study, which was funded by the Wellcome Trust, the Prostate Cancer Foundation and Prostate Cancer UK.
They also found that the drug combination, in addition to killing the cancer cells, slowed their growth.
They found that using either drug alone had no effect on tumor growth.
Since the drugs being tested are in development or already in use for treatment, researchers hope that clinical trials of this combination can begin soon.
Researchers are now seeking funding to advance the drug combination into clinical trials for prostate cancer.
“For men with advanced prostate cancer, once hormone therapy stops working, the outcomes are disappointing,” said Dr Adam Sharp, leader of the Translational Therapeutics Group at The Institute of Cancer Research, London.
“Researchers are constantly discovering new treatment options, but discovering and developing a new drug from scratch is a long process.
“In this work, we examined a large number of drugs that are in development, or already being used to treat cancer.
“We have identified a particularly promising pair that may help patients with advanced prostate cancer, and our data suggest that up to 40 percent of people with this disease may benefit.
“Excitingly, we found that the treatment not only slows tumor growth – it actually kills cancer cells. We are cautiously optimistic that this approach may better prevent treatment resistance from occurring.”
Professor Christian Helin, Chief Executive of The Institute of Cancer Research, London, said: “Finding new ways to overcome treatment resistance is a key priority in cancer research.
“This study highlights how advances can come from re-evaluating existing medicines in innovative ways.
“By identifying the most effective combinations – and, importantly, the ones most likely to benefit patients – we hope to halt cancer progression and give patients more time with their loved ones.”
Commenting on the study, Dr Matthew Hobbs, director of research at Prostate Cancer UK, said: “Prostate cancer kills when it spreads and stops responding to current treatments.
“That’s why the mission to find new ways to target the disease is so urgent – that’s how we’ll save more men’s lives.
“This latest study – led by Dr Juan Vacas, which we funded through a program designed to accelerate the careers of the next generation of researcher leaders – is extremely exciting and could be the next in a series of breakthroughs provided by this team.
“If future research shows that this new treatment approach works in men, it could provide a much-needed new option for men whose cancer has stopped responding to existing treatments, giving real hope to men with advanced prostate cancer.”
According to the National Prostate Cancer Audit, which was released last week, about 58,218 men in England will be diagnosed with prostate cancer in 2024.
And about one in eight (12 percent) men with prostate cancer are not diagnosed until their disease has spread to other parts of the body, also known as metastatic prostate cancer.