REVIEW ON PROSTATE CANCER THERAPY

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About Authors:
Kambham Venkateswarlu1*, G.Sujatha2
1Graduate Student
2Department of Pharmaceutical Chemistry
Sri Lakshmi Narasimha College of Pharmacy, Palluru,
Chittoor District, Andhra Pradesh-517132, India.
*k.v.reddy9441701016@gmail.com

I. INTRODUCTION

1.1.            WHAT IS PROSTATE CANCER?
Prostate cancer is the most common type of cancer in men and is the second leading cause of cancer-related deaths in men worldwide. It is a disease of the prostate gland in which malignant cells form in the tissues of the prostate and multiply out of control. These cells often metastasize to other parts of the body, like the rectum, the bladder and especially, the bones and the lymph nodes. It generally arises near the surface of the gland so that it can be diagnosed easily by digital rectal examination (DRE). Depending on the extent of metastasis, the prostate cancer tissue has been graded using the Gleason System into a score of 2 to 10 or into four stages I-IV (or, A-D), indicating the likelihood of spreading of the disease to other parts of the body.

Although several types of cells are found in the prostate, over 99% of the cancers occur in the gland cells only (cells which make the prostate fluid which is added to the semen). Such type of cancer is termed as adenocarcinoma. The region of prostate gland where the adenocarcinoma is most common is the peripheral zone.  Other types of cancer can also start in the prostate gland, including sarcomas (like leiomyosarcoma and rhabdomyosarcoma), small cell carcinomas, and transitional cell carcinomas, although they are extremely rare. Generally, the cancer grows and spreads very slowly. Early prostate cancer most often causes no symptoms. Sometimes, however there are signs and symptoms very close to those of benign prostatic hyperplasia (BPH).


Reference Id: PHARMATUTOR-ART-1605

1.2. ANATOMY AND FUNCTION OF THE PROSTATE GLAND
The prostate, a part of the male mammalian reproductive system, is a firm, partly glandular, partly fibromuscular body, surrounding the beginning of the male urethra. It lies at a low level in the lesser pelvis, behind the inferior border of the symphysis pubis and pubic arch and anterior to the rectal ampulla, through which it may be palpated. It is an exocrine gland about the size of a walnut and consists of three lobes: one centre lobe with two lobes on each side. The prostate is traversed by the urethra and ejaculatory ducts, and contains the prostatic utricle. The urethra usually passes between its anterior and middle thirds. The ejaculatory ducts pass antero-inferiorly through its posterior region to open into the prostatic urethra.


Figure 1. Location of the prostate in the male reproductive system

As part of the male reproductive system, the primary function of the prostate gland is to secrete a slightly alkaline fluid (pH 7.29) that constitutes 10-30% of the seminal fluid, a fluid that carries sperm. During male climax (orgasm), the muscular glands of the prostate help to propel the prostate fluid, in addition to sperm, that was produced in the testicles, into the urethra.


Valve-less venous communication between the prostatic and extra-dural venous plexuses normally occurs, probably an important factor in the metastasis of prostatic neoplasms to the vertebral bodies.

1.3. EPIDEMIOLOGY OF PROSTATE CANCER:
Prostate cancer is the commonest form of carcinoma afflicting men the world over. In the US, it is the most rampant of all the cases of cancer in men and is the second leading cause of death after lung cancer.

The North American Association of Central Cancer Registries (NAACCR)has estimated that 29% of the incident rates and 9% of the death rates in males from all types of cancer can be attributed to prostatic carcinoma alone. The disease is mainly related to older age as it is mostly diagnosed in men above 40. Also, Asians have the lowest incidence rates of the diseasewhereas the African-Americans are more likely to present with advanced disease than the other races, as per the results of the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute (NCI). 

1.4. SIGNS AND SYMPTOMS OF PROSTATE CANCER
Prostate cancer is most cases it is accompanied by no symptoms at all. The symptoms however are not specific to the disease; they could be caused by an enlarged prostate or BPH and include frequent urination, or weak or interrupted urine flow, pain or burning during urination, blood in the urine or semen, frequent urge to urinate mainly in the night, difficulty in achieving erection or painful ejaculation. Once the cancer has spread to other parts of the body it may manifest itself in the form of bone pain, back pain, urinary and faecal incontinence,weight loss and leg weakness due to compression of the spinal cord by spreading of cancer in the spine.

1.5. PREDISPOSING FACTORS OF PROSTATE CANCER
The specific and exact cause of the disease is still unknown but can be divided into:

1.5.1. Endogenous Factors
a.     Age – The risk of developing prostate cancer increases manifold with advancing age. Men more than 65 years of age are more predisposed to the disease than younger ones. The average age at the time of diagnosis is 70.
b.    Race/Ethnicity – The disease has a high predisposition to racial factors. The African-Americans are at the highest risk whereas Asians are at the lowest risk with the Hispanics and the Whites in between.
c.     Family history - Prostate cancer occurrence has also been demonstrated to have a familial aggregation, with a two to four-fold increased risk of the disease among men who have reported prostate cancer in a close relative like father or brother.
d.    Hormones - Circulating androgens like dihydrotestosterone (DHT) and testosterone probably play an important role in the initiation and promotion of the disease and also in the proliferation of cancerous cells in the prostate cancer.
e.     Genetic Factor – A man’s genetic background also contributes to the risk of developing the disease. About 44% of patients with prostate cancer have a genetic component. Specific genetic lesions resulting in prostate cancer are uncommon though some genes have been implicated in the progress of the disease like the BRCA1, BRCA2 and a high risk gene on chromosome 17p called ELAC2.

1.5.2. Exogenous Factors
a.     Diet – Dietary amounts of certain foods, vitamins, and minerals can contribute to prostate cancer risk. Men with higher serum levels of the short-chain ω-6 fatty acid linoleic acid have higher rates of prostate cancer. Other dietary factors that may increase prostate cancer risk include low intake of vitamin E, omega-3 fatty acids, and selenium.
b.    Environmental agents – Many agents like cadmium, infectious substances and environmental carcinogens have been implicated in the development of the disease. Japanese and Chinese men who live in the West, mainly the US, develop a high rate of the disease than their Asian counterparts.
c.     Medications – There are also some links between prostate cancer and medications, medical procedures, and medical conditions. Daily use of anti-inflammatory medicines such as aspirin, ibuprofen, as also the hypolipidaemic drugs like the statins may decrease prostate cancer risk.
d.    Lifestyle – It has been reported that the degree of sexual activity and/or fertility may govern the risk of developing the disease.

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