Gene Therapy For Prostate Cancer

Gene Therapy For Prostate Cancer

Prostate cancer is by far the most frequently occurring cancer in males with a fairly high morbidity and mortality. Over the years, scientists have developed several meaningful and reliable diagnostic tools and treatment protocols for early detection and treatment. However, almost every treatment procedure is associated with some degree of long term complications. But with the recent success of long term clinical studies on gene therapy; future seems so much brighter today.

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What Is It?

Human immune system serves as a powerful defense system that is capable of identifying and killing any foreign invader. With this unique property, we defeat several disease causing pathogens, viruses, bacterial agents and abnormal cells. However, like all other malignant cells, prostate cancer cells are smart enough to evade host immune defenses via several mechanisms to grow and take over the entire body.

With advances in the immunological sciences, tumor biology and genetic engineering, researchers have successfully developed a system to modify cancer cells into “suicide cells” via “gene therapy”. The aim of this gene therapy is to transform otherw

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ise concealed cancer cells to alert the host immune defenses for attack and destruction.

Several trials are also underway to explore gene therapy via different angles. For example; currently there are 4 categories or classes of gene therapy; depending upon the primary target of immunomodulation. These are:

• Immunomodulatory
• Tumor suppressor gene therapy
• Oncolytic virus therapy
• Antioncogene therapy
• Suicide gene therapy

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Details Of A Suicide Gene Therapy Trial

The first trial was started in 1999 and ended in 2003 with 66 study subjects diagnosed with prostate cancer. As part of the plan, the patient were divided in two groups; arm A receiving gene therapy as well as radiotherapy (with disease confined to prostate gland only) and arm B; receiving hormonal therapy, radiotherapy and gene therapy (with much advanced disease). After the completion of 5-year study period, 97% patients in arm A and 94% of the participants in arm B survived.

Investigators have just finished the second trial in the series (2010 – 2015) and preparations are underway for trial 3. According to the results of the latest phase 2 trials, investigators have established solid evidence that host immune cells can be made to actively attack tumor cells without causing any serious complications on non-tumor cells. Investigators are calling this therapy a unique and promising vaccine that can work with or without hormonal therapy.

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Suicide Gene Therapy – How Does It Works?

Gene therapy involves direct introduction of herpes virus in the prostate cancer cells. Once incorporated in the DNA, the host cancer cells begin to express the enzyme TK or thymidine kinase that directly alerts the host defenses for evasion and destruction. Scientists used adenovirus (the common cold virus) to introduce suicide herpes virus in the prostate patients. To minimize the risk of complications due to herpes virus on the normal cells, investigators administered valacyclovir (the antiviral agent) to the patients after the incorporation of Herpes DNA in cancer cells.

Suicide gene therapy is regarded as ‘the ray of hope’ in the management of prostate cancer in the coming years. Another gene therapy that have been successfully used for prostate cancer management is tumor suppressor gene therapy (3). This involves direct introduction of p53 genes in the prostate cancer cells to cause apoptosis (or natural cell death). Most cancer cells learns how to evade/ turn off p53 genes. Also not every tumor cells expresses p53.

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References

1. B. Teh, H. Ishiyama, W-Y. Mai, T. Thompson, and E.B. Butler. Long-term Outcome of a Phase II Trial using Immunomodulatory In Situ Gene Therapy in Combination with Intensity-Modulated Radiotherapy with or without Hormonal Therapy in the Treatment of Prostate Cancer. Journal of Radiation Oncology; Published online Dec. 12, 2015 (DOI 10.1007/s13566-015-0239-y).

2.  Naitoh, J., & Belldegrun, A. (1998). Gene therapy for prostate cancer. Prostate Cancer & Prostatic Diseases, 1(4).

3. Djavan, B., & Nasu, Y. (2001). Prostate Cancer Gene Therapy—What Have We Learned and Where Are We Going?. Reviews in urology, 3(4), 179.