Aqsa, Jamia Millia Islamia
The Prostate Gland
The prostate is a gland found in men. It is situated just below the bladder or in front of the large part of the rectum. It wraps around the part of the urethra that passes urine and semen out of the body.
What is Prostate Cancer?
Prostate cancer starts in sacs present in the prostate glands that secrete seminal fluid. Cancer cells usually grow from the cells that line the sac. These cancer cells can multiply and form a malignant tumor. Prostate cancer usually grows more slowly than any other cancer in the body.
After the lungs, the male gland most prone to cancer is the Prostate gland. There are four stages of prostate cancer, and it can be cured if detected at an early stage. The four stages are as follows:
- Stage I – In this stage, the tumor remains on only one side of the gland
- Stage II – In this stage, the cancer cells are still inside the prostate gland but have an increased risk of growing to other body parts
- Stage III- In this stage, cancer spreads beyond the outer layer of the prostate
- Stage IV – In this stage, cancer spreads to other parts of the body.
There are various treatments available for its treatment, such as Surgery, Radiation therapy, Hormone therapy, Chemotherapy, Immunotherapy, and Bisphosphonate therapy, etc. A recent study published in the journal eLife inclines on understanding the mechanism of prostate cancer metabolism to produce a therapeutic solution.
Therapeutic Treatment of the disease:
The hormone androgen is necessary for the normal growth and functioning of the prostate gland. This hormone holds equal importance for the tumor to grow. This androgen binds with the androgen receptors, travels to the nucleus, and activates genes that help the tumor to grow. Castration could have been a possible solution, as it will make the tumor cells deprived of androgen. But, studies revealed that after a certain period the tumor cells start producing androgen on their own.
A recent study to understand prostate cancer metabolism at the Flinders University and The University of Adelaide revealed that a feedback loop between the androgen receptor and 6-phosphogluoconate dehydrogenase (6PGD) drives the cancer growth. 6PGD is an enzyme involved in the Pentose Phosphate Pathway and is an androgen-regulated gene. It gets upregulated during prostate cancer, as cancer cells require glucose to produce energy and grow. The researchers found that inhibiting 6PGD can lead to increased oxidative stress, which ultimately leads to the death of cancer cells. Potent inhibitors of 6PGD such as physcion and S3 were tested upon different models of prostate cancer, including the castration-resistant tumors.
6PGD is associated with two important mechanisms that are affected when 6PGD gets inhibited. First, it increases the activity of AMP-activated protein kinase. Second, it is involved in the ubiquitination of the Androgen receptor, resulting in reduced levels of AR.
Conclusion
Hence, understanding this positive feedback mechanism between AR and 6PGD could help in the discovery of new treatments. The growth of prostate cancer cells can be effectively suppressed by co-targeting both AR and 6PGD rather than targeting only one.
This study concluded that potent inhibitors such as physcion and S3 could be used to inhibit 6PGD. It is an enzyme involved in the PPP pathway, inhibiting which can lead to the death of tumor cells. This treatment can now be used as a treatment for even catastrophic resistant prostate cancer.
Also read: Treating degenerative muscle disorders : MyoD and chemicals
References
- Gillis, J. L., Hinneh, J. A., Ryan, N. K., Irani, S., Moldovan, M., Quek, L. E., Shrestha, R. K., Hanson, A. R., Xie, J., Hoy, A. J., Holst, J., Centenera, M. M., Mills, I. G., Lynn, D. J., Selth, L. A., & Butler, L. M. (2021). A feedback loop between the androgen receptor and 6-phosphogluoconate dehydrogenase (6PGD) drives prostate cancer growth. ELife, 10. https://doi.org/10.7554/elife.62592
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