How Hormone Therapy Can Make Prostate Cancer Worse

It is alarming the rate of men suffering from prostate cancer in Nigeria and all over the world. Prostate cancer is a leading cancer diagnosis and cause of cancer related deaths among men. It is the most commonly diagnosed cancer among Nigerian men. From a recent study, an estimated hospital prevalence of 127 per 100,000 in Lagos, Nigeria was reported. A recently published data from southwestern Nigeria also reported a hospital prevalence rate of 182.5 per 100,000 male admissions in the hospital. However, the true prevalence in the Nigerian community is not known. In the United States, prostate cancer has been described to be more prevalent among the African-Americans. The incidence of prostate cancer among Black American men is 405.2 per 200,000 population.

Currently, Medical Scientists at Cedars-Sinai have discovered how prostate cancer can sometimes withstand and outwit a standard hormone therapy, which causes the cancer to spread. Their findings also point to a simple blood test that may help doctors predict when this type of hormone therapy resistance will occur. Prostate Cancer is a slow growing disease that occurs when abnormal cells develop in the prostate. These abnormal cells can continue to multiply in an uncontrolled way and sometimes spread outside the prostate into other parts of the body. It can really affect men because the prostate is directly involved with sexual reproduction, removing it affects semen production and fertility. Radiation therapy affects the prostate tissue and often reduces the ability to father children. The sperm can be damaged and the semen insufficient for transporting sperm. Non-surgical options too, can severely inhibit a man’s reproductive capacity. Options for preserving these functions can include donating to a sperm bank before surgery, or having sperm extracted directly from the testicles for artificial insemination into an egg. However, the success of these options is never guaranteed.

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Prostate cancer is the second-leading cause of cancer death in men, behind lung cancer, killing nearly 75,000 in the Nigeria, each year according to the World Health Organization. In its early stages, the most common type, adenocarcinoma, is curable and generally responds well to therapies, including those that target androgen, a male sex hormone that stimulates tumor growth. However, in certain patients, the cancer becomes resistant to androgen-targeted therapy, and the cancer recurs or spreads. One possible reason for that resistance, from the study, appears to be that the therapy causes some adenocarcinoma cells to become neuroendocrine cancer-type cells – a rare type that normally appears in fewer than one percent of prostate cancer patients.

“This transformation is a problem because neuroendocrine prostate cancer is especially aggressive, metastasizes more readily and is more resistant to both androgen-targeted therapy and chemotherapy. About one-fourth of the patients who receive androgen-targeted therapy may relapse with tumors that show features of neuroendocrine prostate cancer and develop treatment-resistant disease,”

said Neil Bhowmick, PhD,  co-director of the Cancer Biology Program at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai.

To learn more about this process, the researchers examined how cancer cells interact with the supporting cells near the tumor, which was referred to as the tumor microenvironment, in laboratory mice. They found these interactions raised the level of the amino acid glutamine, turning the supporting cells into “chemical factories” that supplied fuel for the cancer cells.

Gottlieb a Professor of Medicine and Vice chair of translational medicine in the Department of Biomedical Sciences at Cedars Sinai stated that;

 “While glutamine is known to spur cancer growth, its role in prostate cancer cells to trigger reprogramming of adenocarcinoma cells into neuroendocrine cancer cells is a new and important finding”.

The research team also examined how androgen-targeted therapy affected the cancer microenvironment. To their greatest surprise, they found out that this type of therapy further changed the cellular environment in a way that caused adenocarcinoma cells in the prostate to transform into neuroendocrine cancer-type cells.

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Concluding the research study with an experiment using mice, the researchers checked the difference in the levels of glutamine in the plasma of small groups of patients, one with treatment responsive prostate cancer and the other with treatment resistant prostate cancer. They found that levels of glutamine were higher in the second group. According to Edwing Posadas MD, co-director of the Translational Oncology Program at the cancer institute and associate professor and clinical chief of the Division of Hematology/Oncology in the Department of Medicine at Cedars-Sinai. This research finding has potential implications for treating prostate cancer patients. The study raises the possibility that a simple blood test measuring glutamine might be able to pinpoint when androgen-targeted therapy is failing in a prostate cancer patient and even predict when therapy resistance will occur, said Posadas, He further stated that the team is designing a new study to test this hypothesis.

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