Scientists may have found the key to weakening prostate cancer cells and boosting treatment effectiveness |

A groundbreaking international study has uncovered a critical vulnerability in prostate cancer cells, offering a promising avenue for more effective treatments. Led by scientists from Flinders University, Australia, in collaboration with South China University of Technology, the research identifies two key enzymes, PDIA1 and PDIA5, that play a vital role in maintaining cancer cell survival and treatment resistance. These enzymes act as molecular chaperones for the androgen receptor (AR), a protein that drives tumour growth. By targeting PDIA1 and PDIA5, researchers were able to destabilise the AR, trigger cancer cell death, and enhance the effectiveness of existing drugs like enzalutamide. This discovery could pave the way for new combination therapies against advanced and resistant prostate cancers, offering hope for improved patient outcomes.

Understanding what keeps prostate cancer cells alive and how key enzymes drive tumour growth

Prostate cancer is the second-leading cause of cancer death in men worldwide, causing significant mortality and morbidity. In the US alone, the American Cancer Society predicts over 313,000 new cases and nearly 36,000 deaths in 2025.

Traditional treatments include surgery, radiation, hormone therapy, and drugs targeting the androgen receptor (AR). While these have extended survival, many patients eventually develop resistance, highlighting the urgent need for novel strategies. Recent research led by Flinders University, Australia, and South China University of Technology identified two enzymes, PDIA1 and PDIA5, as critical supporters of prostate cancer growth. These enzymes act like molecular bodyguards, protecting the androgen receptor, a protein that fuels prostate cancer proliferation.The AR drives the expression of genes that help cancer cells grow, divide, and survive. PDIA1 and PDIA5 stabilise the AR, shielding it from breakdown and helping cancer cells resist existing therapies.Blocking these enzymes has a profound effect: the AR becomes unstable, cancer cells die, and tumours shrink in both lab-grown cells and animal models.

How blocking key enzymes stops cancer growth and energy supply

This newfound vulnerability offers a two-fold advantage for therapy:Destabilising the Androgen Receptor: Without PDIA1 and PDIA5, the AR cannot function properly, weakening cancer growth.Disrupting Cancer Energy Production: The enzymes also support mitochondria, the energy factories of cells. Blocking them leads to oxidative stress and reduced energy, further crippling tumour cells.Professor Jianling Xie from South China University of Technology explained:“It’s like cutting off both the fuel and the engine at the same time, leaving cancer cells unable to survive.”

How enzyme blockers help cancer medicine work better

A major implication of this discovery is the potential to boost existing treatments. When drugs that inhibit PDIA1 and PDIA5 are combined with enzalutamide, a widely used AR-targeting medication, the treatment’s effectiveness significantly improves.Initial tests in patient-derived tumour samples and mouse models showed impressive tumour shrinkage, suggesting this dual approach could be particularly valuable for patients with advanced or treatment-resistant prostate cancer.Professor Luke Selth of Flinders University highlighted:“Targeting these enzymes makes tumours more vulnerable to therapies like enzalutamide, opening the door to more effective treatment strategies.”

PDIA1 and PDIA5 as key targets for cancer cell survival and therapy potential

PDIA1 and PDIA5 are essential not only for AR stability but also for cancer cell survival under stress. Tumour cells often experience high levels of metabolic and oxidative stress due to rapid growth. These enzymes help manage this stress, ensuring the cancer cells can continue to grow.By inhibiting both PDIA1 and PDIA5:

This dual mechanism makes these enzymes particularly promising targets for future therapies.Despite the promise, drugs targeting PDIA1 and PDIA5 are still in early development. Researchers must ensure that these compounds:

Professor Selth cautioned:“While the research is highly encouraging, more studies are needed to confirm safety and efficacy before these therapies can be used in humans.”Also Read | 101-year-old man who survived a coma shares 7 habits to live longer, healthier, and happier every day naturally