Prostate cancer is a malignant disease that affects the male reproductive system. It occurs when there is an uncontrollable growth of the cells in the prostate, a gland located below men’s bladder, near the rectum and around the urethra. Its main purpose is to produce a liquid that is expelled during ejaculation, making the sperm more liquid. Due to the location of the prostate, cancer affects both the urinary and reproductive systems, causing urinary problems such as a slow or weak urinary stream or the need to urinate more often (especially at night), blood in the urine, erectile dysfunction, pain, and weakness or numbness.

Treatment options for patients with prostate cancer include watchful waiting, surgery, radiation therapy, cryotherapy, hormone therapy, vaccine treatment, bone-directed treatment, and chemotherapy, depending on each individual case. Chemotherapy is not the most common treatment used, but it is used to ease patients’ symptoms. The drugs approved in the country for chemotherapy include Docetaxel (Taxotere®), Cabazitaxel (Jevtana®), Mitoxantrone (Novantrone®), Estramustine (Emcyt®), Doxorubicin (Adriamycin®), Etoposide (VP-16), Vinblastine (Velban®), Paclitaxel (Taxol®), Carboplatin (Paraplatin®), and Vinorelbine (Navelbine®).

How Etoposide Works

Etoposide is a medicine included in the class of podophyllotoxin derivatives, since it results from the optimization of the naturally occurring anti mitotic agent podophyllotoxin (PPT), which has interesting properties that lead to the development of anticancer agents. The drug etoposide is used as a chemotherapy in combination with other drugs to treat numerous types of cancer, including ovarian cancer, testicular cancer and prostate cancer. Chemotherapy is usually not used with the purpose of curing prostate cancer, but etoposide is known to be effective in slowing or stopping the growth of cancer cells.

“A semisynthetic derivative of podophyllotoxin, a substance extracted from the mandrake root Podophyllum peltatum,” notes the National Cancer Institute (NCI) Drug Dictionary. “Possessing potent antineoplastic properties, etoposide binds to and inhibits topoisomerase II and its function in ligating cleaved DNA molecules, resulting in the accumulation of single- or double-strand DNA breaks, the inhibition of DNA replication and transcription, and apoptotic cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.”

Etoposide to Treat Prostate Cancer

Etoposide was first approved by the US Food and Drug Administration in 1995 and since then, different drugs have been developed with the compound as active ingredient. For patients with prostate cancer, etoposide is available as capsules to be orally taken once a day for four to five consecutive days. Each cycle may be repeated once every three to four weeks, according to the physician’s recommendations and patient’s response to the medication. Potential side effects associated with the treatment include nausea, vomiting, sores in the mouth and throat, stomach pain, diarrhea, constipation, loss of appetite or weight, unusual tiredness or weakness, pale skin, fainting, dizziness, hair loss, pain, burning, or tingling in the hands or feet, eye pain, and vision problems. However, studies revealed encouraging results regarding the use of etoposide in decreasing the symptoms of prostate cancer.

“Androgen and androgen receptor (AR)-mediated signaling are crucial for the development of prostate cancer. The present study indicates that the topoisomerase II inhibitor etoposide strikingly inhibits androgen/AR-mediated cell growth and androgen-stimulated DNA synthesis in prostate cancer cells. Etoposide significantly repressed the AR mRNA and protein expression in a dose-dependent manner. Etoposide-mediated down-regulation of AR was associated with blocking androgen-induced AR translocation from cytoplasm into nucleus of cells. Additionally, etoposide disrupted the association of AR and heat shock protein 90 and impeded binding of the synthetic androgen [3H]R1881 to AR in LNCaP cells. Etoposide simultaneously reduced the intracellular and secreted PSA levels, a marker for the progression of prostate cancer. These findings collectively reveal that etoposide not only serves as a traditional genotoxic agent but directly targets AR as an AR disrupting therapeutic strategy in prostate cancer,” concluded the authors of the study “Etoposide induces growth arrest and disrupts androgen receptor signaling in prostate cancer cells.”

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