Breakthrough study

A pioneering study by Romie Angelo Azur, Kevin Christian Olarte, Weand Ybañez, Alessandria Maeve Ocampo, and Dr. Pia Bagamasbad at the University of the Philippines (UP) Diliman College of Science National Institute of Molecular Biology and Biotechnology (UPD-CS NIMBB) has identified a key protein, CYB561, that contributes to the progression of prostate cancer into its most aggressive form, NEPC. This discovery elucidates the molecular basis of the disease and opens new avenues for treatment.

According to the World Health Organization, prostate cancer is the third most common cancer type among Filipino men. In 2022, nearly 10,000 Filipino men were diagnosed with this disease. While many cases are manageable, some progress to aggressive forms, such as castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC). NEPC, the most fatal, resists standard treatments.

Standard treatment and limitations

Prostate cancer relies on male sex hormones, or androgens, for growth. Androgen deprivation therapy (ADT) is the standard treatment to stifle this growth. However, over time, cancer cells can mutate, growing without androgens and becoming resistant to ADT, potentially developing into neuroendocrine prostate cancer or NEPC.

A key protein identified
Dr. Bagamasbad and her team discovered that CYB561 plays a dual role in cancer progression: It activates specific growth factors and manages iron levels, enabling cancer cells to thrive even without androgens. Using publicly available data and experimental findings, they found that CYB561 is more prevalent in CRPC and NEPC cells compared to normal prostate cancer cells.

Impact of CYB561 on treatment resistance

Depleting CYB561 made prostate cancer cells more sensitive to enzalutamide, a common ADT drug, suggesting that CYB561 provides resistance to this treatment. The protein also converts iron into a more active form, essential for aggressive cancer cell growth. Knocking down CYB561 reduced active iron levels, delayed CRPC progression to NEPC, and diminished the aggressive behavior of NEPC cells.

Looking forward

The findings, published in PLOS One, could lead to new therapies targeting CYB561. “By understanding the role of CYB561 in prostate cancer,” said Dr. Bagamasbad, “we have potentially identified a new target for future treatments.” The team plans to further research on animal models and primary tumor samples, and investigate whether Filipinos have higher risks of developing CRPC and NEPC due to CYB561. They aim to establish a drug screening platform to target CYB561 activity effectively.

Source: SCIENCE – UP Diliman