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Prostate Cancer and Nanotechnology

Author, Curator: Tilda Barliya, PhD

Prostate cancer  is common and a frequent cause of cancer death. In the United States, prostate cancer is the most commonly diagnosed visceral cancer. In 2012, there were expected to be about 242,000 new prostate cancer diagnoses and about 28,000 prostate cancer deaths. Prostate cancer is second only to nonmelanoma skin cancer and lung cancer as the leading cause of cancer and cancer death, respectively, in US men. Worldwide, in 2008 there were estimated to be 903,000 new cases of prostate cancer and 258,000 prostate cancer deaths making it the second most commonly diagnosed cancer in men and the sixth leading cause of male cancer death (1).

Prostate cancer survival is related to many factors, especially the extent of tumor at the time of diagnosis. The five-year relative survival among men with cancer confined to the prostate (localized) or with just regional spread is 100 percent compared with 31.9 percent among those diagnosed with distant metastases . While men with advanced stage disease may benefit from palliative treatment, their tumors are generally not curable

Prostate-specific antigen (PSA) testing revolutionized prostate cancer screening. Although PSA was originally introduced as a tumor marker to detect cancer recurrence or disease progression following treatment, it became widely adopted for cancer screening by the early 1990s. Subsequently, professional societies issued guidelines supporting prostate cancer screening with PSA. PSA testing led to a dramatic increase in the incidence of prostate cancer, the majority of these newly-diagnosed cancers were clinically localized which led to an increase in radical prostatectomy and radiation therapy, aggressive treatments intended to cure these early-stage cancers (2). However, PSA is also elevated in a number of benign conditions, particularly benign prostatic hyperplasia (BPH) and prostatitis

So what is PSA?

PROSTATE SPECIFIC ANTIGEN (PSA) — PSA is a glycoprotein produced by prostate epithelial cells. PSA levels may be elevated in men with prostate cancer because PSA production is increased and because tissue barriers between the prostate gland lumen and the capillary are disrupted, releasing more PSA into the serum.

A research team led by Prof. Langer and Prof. Farokhzad from MIT and and Brigham and Women’s Hospital in Boston have developed a nanotechnology strategies adopted for the management of prostate cancer. In particular, the combination of targeted and controlled-release polymer nanotechnologies has recently resulted in the clinical development of BIND-14, a promising targeted Docetaxel-loaded nanoprototype, which can be validated for use in the prostate cancer therapy and entered clinical trials in January 2011

The BIND-014 nanoparticles have three components: one that carries the drug (docetaxel), one that targets PSMA, and one that helps evade macrophages and other immune-system cells.

Clinical results

The Phase I clinical trial involved 17 patients with advanced or metastatic tumors who had already gone through traditional chemotherapy. In Phase I trials, researchers evaluate a potential drug’s safety and study its effects in the body. To determine safe dosages, patients were given escalating doses of the nanoparticles. So far, doses of BIND-014 have reached the amount of docetaxel usually given without nanoparticles, with no new side effects. The known side effects of docetaxel have also been milder.

In the 48 hours after treatment, the researchers found that docetaxel concentration in the patients’ blood was 100 times higher with the nanoparticles as compared to docetaxel administered in its conventional form. Higher blood concentration of BIND-014 facilitated tumor targeting resulting in tumor shrinkage in patients, in some cases with doses of BIND-014 that correspond to as low as 20 percent of the amount of docetaxel normally given. The nanoparticles were also effective in cancers in which docetaxel usually has little activity, including cervical cancer and cancer of the bile ducts.

Summary:

Early detection of prostate cancer increased dramatically the five-year survival of patients. “This study demonstrates for the first time that it is possible to generate medicines with both targeted and programmable properties that can concentrate the therapeutic effect directly at the site of disease, potentially revolutionizing how complex diseases such as cancer are treated”. The Phase I clinical trial is still ongoing and continued dose escalation is underway; BIND Biosciences is now planning Phase II trials, which will further investigate the treatment’s effectiveness in a larger number of patients.

REFERENCES

1. Richard M Hoffman. Screening for prostate cancer. http://www.uptodate.com/contents/screening-for-prostate-cancer

2. http://web.mit.edu/newsoffice/2012/cancer-particle-0404.html

3. http://www.bindbio.com/content/pages/news/news_detail.jsp/q/news-id/70

4. State of the art in oncologic imaging of Prostate

http://pharmaceuticalintelligence.com/2013/01/28/state-of-the-art-in-oncologic-imaging-of-prostate/

 

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