Up to Two in Five Advanced Prostate Cancer Patients Could Benefit from Targeted Drug Combination

As the shadows of late-stage prostate cancer loom over tens of thousands of men each year in the UK, a flicker of hope emerges from the laboratories of The Institute of Cancer Research, London. Recent studies reveal that nearly two in five patients battling advanced prostate cancer may find a new lease on life through a promising combination of two targeted drugs. This discovery, which not only slows tumor growth but actively kills cancer cells, has the potential to revolutionize treatment for a disease that often remains stubbornly resistant to conventional therapy.

Targeting Two Proteins

In a groundbreaking study funded by prestigious organizations such as The Wellcome Trust and Prostate Cancer UK, researchers at ICR explored various drug combinations in prostate cancer cells resistant to hormone therapy. The central figures in this investigation are two proteins integral to cancer cell survival: MCL1 and AKT. MCL1 promotes cancer cell longevity, while AKT supports multiple survival mechanisms in tumor cells.

The study, published in Nature Communications, detailed how simultaneously inhibiting both proteins results in prostate cancer cell death. “Targeting cancer at its core could reshape how we approach treatment,” remarked Dr. Adam Sharp, leader of the Translational Therapeutics Group at ICR. “What’s remarkable is that not only do we slow the cancer, but we kill the cells, which could prevent future resistance.”

Drugs Already in Use or Development

The potential breakthrough comes from drugs already in clinical trials for other cancers, including fadraciclib, an MCL1 inhibitor, and AKT inhibitors such as capivasertib and ipatasertib. Researchers cleverly circumvented previous toxicity issues with MCL1 inhibition by indirectly targeting it through CDK9 regulation, a strategy offering new avenues for efficacy and safety.

“Using existing drugs that have shown promise in other contexts allows us to expedite the process of finding effective treatments,” explained Professor Johann de Bono, a leading figure in experimental cancer medicine at the ICR. “We are cautiously optimistic that these discoveries can translate into patient benefits.”

Finding the Right Patients for the Drugs

Not all prostate cancer cells will respond to these treatments; therefore, the team meticulously analyzed various tumor profiles. They found that the combination therapy primarily benefits patients with PTEN-loss and PI3K-activated tumor types—accounting for up to 40% of advanced prostate cancer diagnoses.

• PTEN-loss/PI3K-activated Tumors: This type shows the most significant response to combined treatment.
• Proliferation Rate: In experiments, untreated tumors grew over six times their size in just ten days.
• Programmed Cell Death: Indications suggest that the drug combination activates pathways leading to cancer cell death.

In mouse models with these tumor types, the combination therapy inhibited tumor size expansion effectively. “This is a critical finding,” stated Dr. Juan Jimenez-Vacas, one of the key researchers in the study. “If we can identify the right subset of patients, we can significantly enhance treatment outcomes.”

The Approach May Prevent Resistance Occurring

The researchers are now intensively seeking funding to progress to clinical trials, hopeful that combining these targeted drugs can offer a new strategy to avert treatment resistance—one of the most significant challenges in managing advanced prostate cancer. “Finding effective ways to counteract resistance is crucial not just for extending life but for enhancing quality of life,” said Professor Kristian Helin, Chief Executive of ICR.

Many men diagnosed with advanced prostate cancer face severely limited options once resistance develops to standard hormone therapies. The research reveals that up to 40% of these patients may tap into a new lifeline that simultaneously curtails tumor growth and obliterates malignant cells.

“The overwhelming need for effective treatments can’t be overstated,” remarked Dr. Sharp once more. “This is a game-changing step in our search for alternatives once traditional therapies cease to function.”

As the clock ticks for many men diagnosed with this debilitating disease, the researchers at ICR continue to grasp at the promise of new combinations that could make a profound difference in patient care. The hope is to provide them not just with additional treatment options, but with a fighting chance in an uphill battle—one fortified by innovation and collaboration across scientific disciplines.

Source: www.icr.ac.uk