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MANILA, Philippines — Scientists from the University of the Philippines Diliman (UPD) have identified a key protein in patients diagnosed with a form of prostate cancer that is resistant to treatment, providing them with vital data that may lead to new ways to manage one of the most common cancers among men worldwide.
In a pioneering study, researchers Romie Angelo Azur, Kevin Christian Olarte, Weand Ybañez, Alessandria Maeve Ocampo and Dr. Pia Bagamasbad of the UPD College of Science-National Institute of Molecular Biology and Biotechnology (NIMBB) found that a protein called cytochrome b561 (CYB561) was pivotal in the progression, growth and survival of aggressive and treatment-resistant prostate cancer cells.
“CYB561 has a dual role in driving cancer,” said Bagamasbad, who is also the NIMBB director. “It activates specific growth factors and manages iron levels, both of which appear to help the cancer thrive and grow even when deprived of the male hormones it usually depends on.”
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“By understanding the role of CYB561 in prostate cancer, we have not only gained a deeper understanding of how prostate cancer develops drug resistance but we have also potentially identified a new target for future treatments, paving the way for novel therapies that could specifically inhibit CYB561’s activity to slow down or stop cancer progression,” she added.
According to the World Health Organization, prostate cancer is the third most common type of cancer among Filipino men, after lung cancer and colorectal cancer. In 2022 alone, there were almost 10,000 cases and 3,850 deaths, making it the ninth most deadly cancer in the Philippines.
Androgen-dependent
The development of prostate cancer is dependent on androgen, the male sex hormone. When cancer cells do not have access to this hormone, their growth is stunted, making androgen deprivation therapy (ADT) the standard treatment for the disease.
But over time, cancer cells may mutate in ways that allow them to grow even without androgen. This may lead to prostate cancer patients developing more aggressive forms of the disease that are ADT-resistant: castration-resistant prostate cancer (CRPC) or rare neuroendocrine prostate cancer (NEPC). CRPC can shorten a patient’s life by two years, while those with NEPC are given less than a year to live.
Using publicly available data from prostate tumors and experimental findings from human cell culture lines, the UPD scientists found that the protein CYB561 was more prevalent in CRPC and NEPC cells compared with primary prostate cancer cells.
They also discovered that after eliminating CYB561, the prostate cancer cells became more sensitive to enzalutamide, a common ADT drug, suggesting that the protein contributed to resistance to treatment.
‘Other key players’
Another vital finding was that CYB561 converts iron into a more active form essential for various cell processes, including promoting the growth of aggressive forms of cancer.
Reducing the protein’s levels showed three positive effects: it lowered the active iron levels in NEPC cells, delayed the progression of CRPC to NEPC, and dampened the highly aggressive behavior of NEPC cells.
The findings of the UPD team, which were published in the PLOS (Public Library of Science) One peer-reviewed journal in May, are seen to lead to the development of new therapies for CRPC and NEPC.
The researchers are now looking at experimenting with CYB561 on animal models and primary tumor samples. They also plan to examine whether Filipinos have a higher risk of developing CRPC and NEPC, and if CYB561 contributes to the aggressiveness of the disease.
“More importantly, we need to identify other key players involved and establish a drug screening platform that can mechanistically target CYB561 activity,” Bagamasbad said.