IJPCBS 2013, 3(1), 185-199 Lalla et al. ISSN: 2249-9504

INTERNATIONAL JOURNAL OF PHARMACEUTICAL, CHEMICAL AND BIOLOGICAL SCIENCES

Available online at www.ijpcbs.com Review Article

PROSTATE CANCER

JK. Lalla*, Sunita Ogale2, Vikram Gota3 Meena Shah4 and Deven Parmar5 Sanskruti, 20 / 701-702, Thakur Complex, Kandivli (E), Mumbai, Maharashtra, India.

INTRODUCTION secreted into prostatic fluid and semen, The two Articles published earlier by us small amounts of PSA are present in were number one is on general cancer blood.[See fig. no. 1 which depict the &second is on breast cancer. In continuation Anatomy of Prostate gland] with this, we would like to emphasis on here.

Anatomy, Physiology &Pathophysiology ofProstate gland1,1a The prostate gland is present only in males, although females have homologous glands (having the same embryological origin) around the urethra; these are called 'Skene's glands' or 'the female prostate'. The prostate gland surrounds the proximal part of the urethra as it exits the base of the Fig. 1: Anatomy of prostate gland© 2009 bladder.The size of the prostate varies with WebMD, LLC. age ranging from size of a walnut, but it can Several types of cells are found in the be much larger in older men.It produces prostate, but almost all prostate cancers fluid that protects and nourishes sperm developfrom the glandularcells. Glandular cells in semen, making the semen fluid. cells make the prostate fluid that is added to Semen is a gray and rather opalescent, the semen. The medical term for a cancer turbid fluid having pH of 7.2 to 8.0.Life & that starts in glandular cells is movement of sperms depends on important adenocarcinoma. properties of semen.A groove down the Other types of cancer can also start in the centreof the prostate gland divides it into prostate gland, including sarcomas, small left and right lobes. cellcarcinomas, and transitional cell Anatomists more precisely describe the carcinomas. But these types of prostate prostate gland as having anterior, posterior, cancer are sorare that if you have prostate lateral, and median lobes, whereas cancer it is almost certain to be an pathologists sometimes describe the adenocarcinoma. prostate as having zones (peripheral, Some prostate cancers can grow and spread central, transitional, periurethral, and quickly, but most grow slowly. In fibromuscular). The peripheral zone fact,autopsy studies show that many older accounts for most of the prostate gland and men (and even some younger men) who about 75% of prostate cancers. died ofother diseases also had prostate Fluid secreted by the prostate forms about cancer that never affected themduring their 30% of the volume of semen. lives. Inmany cases neither they nor their PSA is a produced by normal and doctors even knew they had it. cancerous prostate cells.

PSA is secreted by prostate epithelial cells Microscopic Anatomy into prostatic fluid, where its function is to Historically, the prostate has been divided liquefy semen and thus allow spermatozoa into 3 zones: (1) transition zone, (2) central to move more freely. Although PSA is

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zone, and (3) peripheral zone. The where 70% of adenocarcinomas are found. transition zone accounts for 10% of the This area is also the location most prostatic glandular tissue and 20% of the commonly affected by chronic prostatitis. adenocarcinomas.The prostate consists of approximately 70% glandular tissue and Possible pre-cancerous conditions of the 30% fibromuscularstroma. prostate Prostate cancer maystarts out as a following Transition zone pre-cancerous condition, The prostatic urethra courses the length of the prostate from the level of the bladder Prostatic intraepithelial neoplasia (PIN) neck to the level of the membranous In this condition, there are changes in how urethra. The epithelium consists of the prostate gland cells look under transitional cells similar to bladder themicroscope, but the abnormal cells don't epithelium. This transitional zone is where look like they are growing into other parts benign prostatic hyperplasia occurs and can of theprostate (like cancer cells would). lead to bladder outlet obstruction when an Based on how abnormal the patterns of adenoma grows to a significant size. When cells look, they are classified as: the adenoma grows large enough, it can [a] Low-grade PIN: the patterns of prostate compress the fibromuscular band cells appear almost normal. surrounding this zone, creating a surgical [b] High-grade PIN:the patterns of cells look capsule. more abnormal. The transitional zone is often described as having 2 lateral lobes and a median lobe Proliferative inflammatory atrophy that lead to the symptoms of the lower (PIA) urinary tract symptoms. A urethral crest This is another finding that may be noted on runs along the posterior midline and a prostate biopsy.In PIA, the prostate disappears at the membranous urethra. On cellslook smaller than normal, and there are both sides of the urethral crest, there is a signs of inflammation in the area. PIA is grove where the prostatic sinuses exist and notcancer, but researchers believe that PIA drain all of the glandular elements. may sometimes lead to high-grade PIN, The urethral crest widens and protrudes orperhaps to prostate cancer directly.[See from the posterior wall as the seminal fig. no. 2] colliculus (verumontanum). A small midline Changes taking place during the prostate pit, the prostatic utricle, is found at the apex cancer are depicted in Figure 2 of the seminal colliculus. On either side of the utricular orifice, the small slitlike openings to the ejaculatory duct can be found.

Central zone The central zone is the area surrounding the ejaculatory ducts. This zone consists of 25% of the glandular tissue. Very few adenocarcinomas are found in this region and can represent as little as 1-5% of these tumors in the prostate.

Peripheral zone http://www.elsevierimages.com/images/vt The peripheral zone of the prostate n/000/000/027/27881-150x150.jpg constitutes 70% of the glandular tissue. Fig. 2: Proliferative inflammatory atrophy This zone covers the posterior and lateral (PIA) as a precursor to prostatic aspects of the prostate. The peripheral zone intraepithelial neoplasia (PIN) and prostate is the area that is palpated on digital rectal cancer. (Adapted from Nelson WG, DeMarzo examination (DRE) and represents the area

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AM, Isaacs WB: Prostate cancer. N Engl J of prostate cancer by increasing Med 2003;349:366–381.) levels for the cancer cells to use to survive and grow; PSMA increases available Pathophysiology of prostate cancer 2 for use by hydrolyzing glutamated-folates. Prostate cancer is classified as an adenocarcinoma, or glandular cancer, that IMPORTANCE OF AWARENESS3 begins when normal semen-secreting Although there is growing awareness about prostate gland cells mutate into cancer cells. women-affecting cancers like cervical and The region of prostate gland where the breast cancer, male-centric tumours are adenocarcinoma is most common is the usually given step-motherly treatment. peripheral zone. Initially, small clumps of Despite the high-incidence of prostate cancer cellsremain confined to otherwise cancer normal prostate glands, a condition known among men in the age group of 55-60 years as carcinoma in situ or prostatic in united states, there is no documented intraepithelial neoplasia (PIN). Although data to understand its prevalence in india. there is no proof that PIN is a cancer As men aged over 50 years are at high risk precursor, it is closely associated with from the disease, it is advisable for anyone cancer. Over time, these cancer cells begin over that age to undergo check-up as the to multiply and spread to the surrounding disease is easier to cure,if detected early. To prostate tissue (the stroma) forming a spread awareness about the disease, free tumor. Eventually, the tumor may grow prostate cancer awareness camp shall be large enough to invade nearby organs such organized by government & non- as the seminal vesicles or the rectum, or the government organizations. tumor cells may develop the ability to travel Early diagnosis is the key to beat prostate in the bloodstream and lymphatic system. cancer. Educational programs can increase Prostate cancer is considered a malignant the awareness and use of cancer screening. tumor because it is a mass of cells that can invade other parts of the body. This PROSTATE CANCER STATISTICS IN invasion of other organs is called INDIA4 metastasis. Prostate cancer most commonly Prostate cancer incidence is increasing in metastasizes to the bones, lymph nodes, India by 1% every year. The average age rectum, and bladder. The prostate is a adjusted incidence rates for prostate cancer accumulating, citrate producing organ. The in Indian registries are ranged from protein ZIP1 is responsible for the active 4.1/100,000 for Chennai registry to transport of zinc into prostate cells. One of 8.1/100,000 for Delhi registry, incidence zinc's important roles is to change the rate of 6.3/100,000 at Mumbai registry and metabolism of the cell in order to produce at Bangalore registry it is 5.6/100,000 in citrate, an important component of semen. 2002-03. The process of zinc accumulation, alteration Cancer Registries are under the network of of metabolism, and citrate production is National Cancer Registry Programme energy inefficient, and prostate cells (NCRP) of Indian Council of Medical sacrifice enormous amounts of energy Research (ICMR), New Delhi. The Cancer (ATP) in order to accomplish this task. Registry has been collecting all essential Prostate cancer cells are generally devoid of data pertaining to cancer patients, in the zinc. This allows prostate cancer cells to resident population of the respective areas. save energy not making citrate, and utilize The registry collects information, analyzes the new abundance of energy to grow and it, and produces a report which is presented spread. The androgen receptor helps to the Indian Council of Medical prostate cancer cells to survive and is a Research.This report presents information target for many anti cancer research like number of cancer cases registered, studies; so far, inhibiting the androgen cancer rate in men, women and children, receptor has only proven to be effective in number of deaths registered due to cancer, mouse studies. Prostate specific membrane common cancer site in men, common cancer antigen (PSMA) stimulates the development site is women etc which in turn helps to

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plan the various prevention, awareness, Recently, some common variations curative programs. have been linked to a higher risk of prostate cancer. IMPORTANCE OF PROSTATE CANCER ON BASIS OF GLOBAL STATISTICS5 Diet-There appears to be a link with people More than 241,000 men will be diagnosed living in urban areas exposed to pollution with prostate cancer in 2012 and 28,170 and those consuming large quantities of will die from the disease,in USA according dietary fat. Lower blood levels of vitamin D to an estimate by the National Cancer may increase the risk of developing prostate Institute. cancer. 1 in 6 men will be diagnosed with prostate cancer.1 in 10,000 under age 40 will be Obesity- Some studies have found that diagnosed, the rate shoots up to 1 in 39 for obese men have a lower risk of getting a ages 40 to 59, and 1 in 14 for ages 60 to 69. low-grade (lessdangerous) form of the In fact, about 65% of all prostate cancers disease, but a higher risk of getting more are diagnosed in men over the age of 65. aggressive prostate cancer.

RISKFACTORS6 Inflammation of the prostate- Some Age-Although men of any age can get studies have suggested that prostatitis prostate cancer,age is the strongest risk (inflammation of the prostate gland) may factor. Over 80% of prostate cancer belinked to an increased risk of prostate diagnoses occurring in men older than age cancer; Inflammation is often seen in 65 years. The degree to which the incidence samples of prostate tissue that also contain of prostate cancer increases exponentially cancer. Thelink between the two is not yet with age is greater than with any other clear, but this is an active area of research. cancer. Autopsy studies found that as many as 75% of men older than age 85 years have Sexually transmitted infections- prostate cancer at the time of death. Researchers have looked to see if sexually transmitted infections (like gonorrhea, Family history- Having a first-degree orchlamydia) might increase the risk of relative with a history of prostate cancer prostate cancer, possibly by leading increases the risk two- to three-fold. toinflammation of the prostate. However; the exact responsible for the development of prostate cancer are not Vasectomy- Some earlier studies had known. suggested that men who have had a vasectomy (minor surgery tomake men Ethnic/racial background- African- infertile) – especially those younger than 35 American men are 1.6 times more likely to at the time of the procedure – mayhave a develop prostate cancer compared with slightly increased risk for prostate cancer. Caucasian men, and are nearly 2.4 times as But most recent studies have not foundany likely to die from the disease. It is rare increased risk among men who have had among the Chinese. this operation.

Other potential risk factors- The PROGNOSIS7 endogenous levels of androgens and other Prostate cancer rates are higher in hormones (vitamin D levels, insulin-like developed countries than in the rest of the growth factors), inflammation, and world. Many of the risk factors for prostate vasectomy status may also be associated cancer are more prevalent in the developed with prostate cancer risk. world, including longer life expectancy and diets high in red meat.Also, where there is Genes- Scientists have found few inherited more access to screening programs, there is gene changes that seem to raise prostate a higher detection rate. Prostate cancer is cancerrisk, but they account for a very small the ninth-most-common cancer in the percentage of prostate cancer cases. world, but is the number-one non-skin

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cancer in men from the United States.In studied further to see how quickly the India in the 1990s, half of the people with cancer will spread. prostate cancer confined to the prostate This measure is known as the Gleason died within ten years.African-American men score. The lower the score, the less likely have 50–60 times more prostate cancer and the cancer will spread. prostate cancer deaths than men in  A Gleason score of 6 or less means the Shanghai,China&Nigeria.In patients who cancer is unlikely to spread. undergo treatment, the most important  A Gleason score of 7 means that there is clinical prognostic indicators of disease a moderate chance of the cancer outcome are stage, pre-therapy PSA level, spreading. If the biopsy shows the and Gleason score. In general, the higher the presence of cancer, patient may need grade and the stage, the poorer the more tests to see if the cancer has prognosis. spread.  Imaging tests -- computerized DETECTION AND DIAGNOSIS8,8a tomography (CT) or magnetic There is no single test to diagnose prostate resonance imaging (MRI) scans may cancer. The main tests include: pinpointthe location of cancer that has  A urine test to rule out a urine infection spread beyond the prostate.  Digital rectal exam (DRE) -- in this test,  Bone scans and x-rays -- these tests look the doctor inserts a gloved, lubricated for spread of cancer to the bones. finger into the rectum in order to feel  Lymph node biopsy -- a surgical the prostate for bumps or other procedure to find out if the cancer has abnormalities. Many malignant tumors spread to the lymphatic system. begin in the outer part of the prostate and may be found with this exam. Some Stages of Prostate Cancer men find this test embarrassing, but it is The clinical stage of cancer is important in quick,relatively painless, and helps find choosing a treatment. The clinical stage tells many prostate cancers. how much the cancer may have grown  PSA test -- a blood test measuring the within the prostate and whether it has level of prostate-specific antigen (PSA). spread to other tissues or organs. In case of Prostate cancer cells produce higher surgery, lymph nodes, and seminal vesicles amounts of PSA, so measuring PSA nearby prostate will be removed and levels may help find cancer while it is samples of them studied under a still microscopic. However, finding microscope. This exam gives the pathologist elevated levels of PSA does not always the information to find out the pathological mean that a man has cancer. Benign stage toone’s cancer. Based on this doctor conditions such as an enlarged prostate may do one or more of the following tests or can also elevate PSA levels.If either the exams to help figure out the stage of cancer: DRE or PSA test suggests that cancer  DRE might be present, doctor may  Prostate biopsy recommend the followingtests:  Bone scan  Transrectal ultrasound -- using a small  MRI probe inserted into the rectum, sound  CT scan waves help get a visual imageof the  Biopsy of the lymph nodes in the pelvis prostate.  Biopsy of the seminal vesicles  Biopsy of the prostate -- a tissue sample is obtained through the rectum and Tumor Stages examined for cancerous cells. Prostate cancer is typically staged according to the American Joint Committee on Gleason score Cancer’s tumour, node, metastasis (TNM) The samples of tissue from the biopsy are system, in which the tumour stage (T) is then studied in microscopically. If based on the extent of penetration or cancerous cells are found, they can be invasion beyond the prostatic capsule into adjacent structures (Table 1). Localized

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prostate cancer is classified as stages T1 is associated with the presence of more (non-palpable) and T2 (palpable) and is poorly differentiated cells and other confined within the prostatic capsule. The histopathologic features. likelihood of progression to invasive cancer

Table 1: Showing Prostate Cancer Tumor Staging* Tumor Description Stage TX Primary tumor cannot be assessed T0 No evidence of primary tumor Clinically unapparent tumor not palpable or visible by imaging T1a: Tumor incidental histologic finding in ≤5% of tissue resected T1b: Tumor incidental histologic finding in T1 >5% of tissue resected T1c: Tumor identified by needle biopsy (e.g., because of elevated PSA levels) Tumor confined within prostate T2a: Tumor involves 50% of one lobe or less T2b: Tumor T2 involves >50% of one lobe but not both lobes T2c: Tumor involves both lobes Tumor extends through the prostate capsule T3 T3a: Extracapsular extension (unilateral or bilateral) T3b: Tumor invades seminal vesicle(s) Tumor is fixed or invades adjacent structures other than seminal vesicles: bladder neck, T4 external sphincter, rectum, levator muscles, and/or pelvic wall * From the American Joint Committee on Cancer.

According to the National Institute of Information flows in a cell from cancer, T1 means that the cancer is so small DNA RNA Protein. A rearrangement it can’t be felt during a DRE. T1a and T1b or translocation of results in cancer is most often found by accident, two abnormally fused genes whose when men have surgery to relieve abnormal RNA and protein products put symptoms of BPH (benign prostatic cells on the path to cancer. Such gene hyperplasia). fusions are commonly found in human T1c is most often found when a prostate cancers such as prostate and leukemia. biopsy is done because of a PSA test result Researchers have identified abnormal RNA that showed a high PSA blood level. This is fusions that were generated without any the most commonly diagnosed stage of changes to their corresponding genomic prostate cancer. DNA by a mechanism they’ve dubbed “cis- A stage of T2 means that prostate cancer splicing of adjacent genes,” or cis-SAGe, for can be felt during a DRE, but is still only in short. the prostate. The stage may be a, b, or c, When analyzing the prostate cancer cell depending on the cancer’s size and whether lines, Dr.Hui Li and his team found fusions it is in 1 or more lobes of the prostate. in the RNA products of the SLC45A3 and ELK4 genes located adjacent to each other IN-VITRO DETECTION on 1. They showed that this Prostate cancer cell lines9.9a SLC45A3-ELK4 RNA fusion transcript was Cell lines are widely used in many aspects of generated by an aberrant read-through of laboratory research and particularly as in the two genes, when the message should vitro models in cancer research. They have have stopped transcribing after the first number of advantages; for example, they gene. This aberrant read-through was are easy to handle and represent an termed cis-SAGe.Li and his team observed unlimited self-replicating source that can be that SLC45A3-ELK4 fusion RNA promoted grown in almost infinite quantities. They cancer cell growth in vitro and that the represent a relatively high degree of levels of SLC45A3-ELK4 fusion RNA in homogeneity and are easily replaced from human prostate samples correlated with frozen stock if lost through contamination. disease progression—non-cancerous However cell lines that have been deposited prostate tissue had the lowest levels of for long period in banks may prone to SLC45A3-ELK4 fusion RNA; men with genotypic and phenotypic drift during their metastatic prostate cancer had the highest. continual culture. The new cell lines are the first available derived from a bone metastasis of an

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androgen-independent prostatic market and UNeMed currently offers a adenocarcinoma that grow both in vivo and variety of licensing options and in vitro and have retained PSA expression collaborative development opportunities and androgen sensitivity. Scientists with the University of Nebraska Medical developed a novel cell line which mimics Center. the stages of resistance to androgen therapy Cell lines are marketed by ---- American for study of the molecular mechanisms by Type Culture Collection [ ATCC], Life which androgen therapy sensitive prostate technologies& others. cancer cells differentiate to androgen resistant cancer cells. This technology will SIGNS AND SYMPTOM10 allow the generation of entirely novel Many men with prostate cancer often have methods for screening, treatment and no symptoms. If symptoms appear, they prevention of androgen resistant prostate include: cancer. These cell lines are available in

Table 2: Describes signs & symptoms Blood in the urine The need to urinate frequently, especially at night Weak or interrupted urine flow Pain or burning feeling while urinating The inability to urinate Constant pain in the lower back, pelvis, or upper thighs Painful ejaculation.

CENTRES FOR DETECTION & DIAGNOSIS given certain exams and tests, including IN INDIA biopsies, on a regular schedule.

Dharamshila Hospital ------Chemotherapy Delhi Chemotherapy is a cancer treatment that Indian Cancer Society------uses drugs to stop the growth of cancer Mumbai cells, either by killing BGS Global Hospital ------the cells or by stopping them from dividing. Bangalore When chemotherapy is taken by mouth or DeenanathMangeshkar Hospital & Res. injected into a vein Centre ------Pune or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the TYPES OF TREATMENT11,11a body (systemic Different types of treatment are available chemotherapy). When chemotherapy is for patients with prostate cancer. Some placed directly into the cerebrospinal fluid, treatments arestandard (the currently used an organ, or a body treatment), and some are being tested in cavity such as the abdomen, the drugs clinical trials. mainly affect cancer cells in those areas Six types of standard treatment are used. (regional chemotherapy).

Watchful waiting or active surveillance Biologic therapy Watchful waiting is closely monitoring a Biologic therapy is a treatment that uses the patient’s condition without giving any patient’s immune system to fight cancer. treatment until symptoms Substances made appear or change. by the body or made in a laboratory are Active surveillance is closely following a used to boost, direct, or restore the body’s patient's condition without giving any natural defenses treatment unless there are against cancer. This type of cancer changes in test results. It is used to find treatment is also called biotherapy or early signs that the condition is getting immunotherapy. Sipuleucel-T is worse. In active surveillance, patients are

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a type of biologic therapy used to treat lasts about 15 minutes. prostate cancer that has metastasized 3-D conformal radiation therapy is a (spread to other parts of the type of external beam radiation that is body). often used to treat prostate cancer. It allows doctors to carefully plan the Hormone Therapy shape of the radiation beam so it targets Male sex hormones, such as testosterone, the cancer more precisely, while can help prostate cancer grow. Hormone avoiding healthy tissues nearby. therapy slows prostate cancer’s growth by  Brachytherapy- is a type of internal reducing the body’s ability to make radiation therapy in which a doctor testosterone or by blocking testosterone’s places radioactive material inside the action in prostate cancer cells. prostate. Brachytherapy is a choice for Hormone therapy used in the treatment of men with low-risk prostate cancer. prostate cancer may include the following : There are two main types of  Luteinizing hormone-releasing brachytherapy used for prostate cancer, hormone agonists can prevent the low-dose rate (also called LDR) and testicles from making testosterone. high-dose rate (also called HDR). Examples are leuprolide, goserelin, and  LDR brachytherapy- In this type of buserelin. brachytherapy, a doctor will place low-  Antiandrogens can block the action of dose sources of radiation, or seed androgens (hormones that promote implants, throughout your prostate. male sex characteristics).Examples are Each seed implant is smaller than a enzalutamide, flutamide, and grain of rice. The number of seeds will nilutamide. depend on the size of your prostate. The  Drugs that can prevent the adrenal radiation will get weaker each day and glands from making androgens include run out in 2 to 10 months. ketoconazole and aminoglutethimide.  HDR brachytherapy- Before treatment  Orchiectomy is a surgical procedure to starts, a doctor will place tiny catheters remove one or both testicles, the main (hollow tubes) throughout prostate. For source of male hormones, to decrease each treatment, the doctor will place 1 the amount of hormone being made. or more sources of high-dose radiation  Estrogens (hormones that promote in the prostate through the catheters. female sex characteristics) can prevent Then, radioactive material will be the testicles from making testosterone. removed after a few minutes. The However, estrogens are seldom used catheters will remain in place for the today in the treatment of prostate entire course of treatment.The catheters cancer becauseof the risk of serious side will be removed, once treatment is over. effects. External beam radiation therapy and brachytherapy can be used together. Radiation Therapy This type of treatment uses high doses of Surgery radiation energy to treat cancer. Radiation Surgery is a treatment choice for men with therapy is a good choice with early-stage early-stage prostate cancer who are in good prostate cancer. It is also the best treatment health. Surgery to remove the prostate is for older men or those who have other called prostatectomy. There are different health problems. There are different types types of surgery for prostate cancer. They of radiation therapy: include:  External beam radiation- In this type  Open prostatectomy. Also called of radiation therapy, a machine aims retropubic prostatectomy. In this radiation at cancer.The machine moves surgery, the prostate is removed around body, sending radiation from through a single long cut made in many directions. The treatment once a abdomen from a point below navel to day, 5 days a week, for 6 to 9 weeks may just above the pubic bone. This type of be given. Each treatment session usually surgery can be used for nerve-sparing

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surgery. Nerve-sparing surgery lessens DRUG DISCOVERY RESEARCH the chances that the nerves near your &RECENTLY DISCOVERED prostate will be harmed. These TREATMENTS12,12a,12b,12c important nerves control erections and Discovery and development of anti- normal bladder function. canceragents are the key focus of several  Laparoscopic surgery. In this type of pharmaceutical companies as well as non- surgery, uses a laparoscope to see and profitgovernment and non-government remove the prostate. This surgery is organizations, like the National Cancer done through 4 to 6 small cuts in the Institute (NCI) in the United States, the navel and the abdomen. European Organization for Researchand Treatment of Cancer (EORTC), and the  Perineal prostatectomy. In this type British Cancer Research Campaign(CRC). the prostate is removed through an The pharmaceutical industry is increasingly incision between scrotum and anus. looking for ways to speed development of This type of surgery is not used very new drugs. often. The Institute of Cancer Research, London, and its partner hospital The Royal Marsden New types of treatment are being tested NHS Foundation Trust jointly led the new in clinical trials. Phase III trial of enzalutamide and the Cryosurgery Phase III trials of two other drugs, Cryosurgery is a treatment that uses an cabazitaxel and abiraterone. Drug instrument to freeze and destroy prostate enzalutamide can significantly extend life cancer cells. This type of treatment is also and improve quality of life in men with called cryotherapy. advanced prostate cancer. The drug, Xtandi (enzalutamide) made by pharmaceutical High-intensity focused ultrasound companies Medivation and Astellas, could High-intensity focused ultrasound is a be licensed for use by British patients early treatment that uses ultrasound (high- next year,2013.The US Food and Drug energy sound waves) to destroy cancer Administration (FDA) announced that cells. To treat prostate cancer, an endorectal Xtandi has been approved for men with probe is used to make the sound waves. metastatic castration-resistant prostate cancer that has recurred or spread, Proton beam radiation therapy regardless of whether patients received Proton beam radiation therapy is a type of medical or surgical therapy to reduce high-energy, external radiation therapy that testosterone levels. targets tumors with streams of protons Progenics Pharmaceuticals Inc. has opened (small, positively charged particles). This enrollment in a Phase 2 study in prostate type of radiation therapy is being studied in cancer patients of its PSMA ADC compound. the treatment of prostate cancer. PSMA ADC is a targeted anti-cancer therapeutic that uses a monoclonal Medication antibody to deliver a cell-killing drug to List of medicines used to treat prostate malignant cells. cancer and approved by FDA. According to a report issued by PhRMA Finasteride (formerly known as the Pharmaceutical Degarelix Research and Manufacturers Association), Jevtana (Cabazitaxel) there are approximately 80 drugs currently Lupron (Leuprolide Acetate) in clinical development for the treatment of Xtandi (Enzalutamide) prostate cancer. Zytiga (Abiraterone Acetate) Gamma-Tocotrienol Kills Prostate Cancer Prednisone Stem Cells. A study reveals that gamma- Provenge (Sipuleucel-T) tocotrienol is effective in targeting prostate Taxotere (Docetaxel) cancer stem cells, offering a potential means Viadur (Leuprolide Acetate) to prevent cancer growth and disease relapse.

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Scientists from Singapore, Australia and their colony formation capability. This Hong Kong have found that gamma- results in a lower prostate cancer stem cell tocotrienol is potent in killing prostate population (as defined by the protein cancer stem cells. This small group of cells markers CD133 and CD44). is responsible for the initiation of prostate Further tests in mice models were cancer and is resistant to conventional conducted, where mice implanted with chemotherapy drugs. It causes relapses in hormonal refractory prostate cancer cells the cancer by producing new chemo- were given gamma-tocotrienol orally. The resistant cancer cells. Gamma-tocotrienol is results showed that gamma-tocotrienol not a member of the Vitamin E family and is only reduced tumour size formed, but also derived naturally from palm oil. This study decreased the incidence rate of tumour aimed to find a way to eradicate prostate formation by 75%, as compared to the cancer stem cells. It follows an earlier control group of mice, which had 100% report that demonstrated the effectiveness tumour formation. These results strongly of gamma-tocotrienol in targeting the bulk suggest that gamma-tocotrienol could be of the prostate tumour mass. This latest developed for prostate cancer prevention finding highlights the considerable potential and treatment. "Current chemotherapy of gamma-tocotrienol as a natural remedy drugs, such as Docetaxel, have limited effect to prevent and treat prostate cancer. on prostate cancer stem cells, although they The scientists found that low doses of are currently the first-line drug given to gamma-tocotrienol cause apoptosis in the patients with advanced hormonal refractory prostate cancer stem cells and suppress prostate cancer.

Table 3: illustrates products under development by leading pharma companies Pharmaceutical company New molecule Use Centocor Ortho Biotech Siltuximab hormone-refractory prostate cancer Novartis Pharmaceuticals Imatinib prostate cancer Bristol-Myers Squibb Ipilimumab prostate cancer NewLink Genetics Prostate cancer vaccine hormone-refractory prostate cancer Johnson & Johnson JNJ-26854165 prostate cancer Abbott pharmaceuticals leuprorelin depot (6-month formulation) prostate cancer IncuronBuffalo mepacrine hormone-refractory prostate cancer Molecular Insight MIP1095 and radiolabelled diagnostic diagnosis of prostate cancer PolyphenonPharma polyphenonE prostatic intraepithelialneoplasia DendreonSeattle Sipuleucel-T androgen-dependent recurrent prostate cancer Amgen Rilotumumab early stage prostate cancer Genta Tesetaxel advanced prostate cancer OncoGenex Pharmaceuticals custiren prostate cancer AstraZeneca Zibotentan castration-resistant prostate cancer

New Dosage Forms system, the temperature induced by the Magnetic nanoparticles (MNPs) and magnetic core would be used to release polymer magnetic nanoparticles (PMNPs) therapeutic agents from the polymer shell have been attracting a great amount of at a specific location. The chemical and attention because of their numerous physical properties of these PMNPs were applications including contrast agents in determined using Fourier transformed magnetic resonance imaging (MRI), infrared spectroscopy, nuclear magnetic magnetic targeted drug carriers, and resonance, x-ray photoelectron hyperthermia treatments for cancer. spectroscopy, and a superconducting Researcher have developed the polymer quantum interference device. magnetic nanoparticles (PMNPs) using a silane coupling agent and a novel thermo- COMPLEMENTARY AND ALTERNATIVE sensitive polymer, N-isopropylacrylamide- THERAPIES13 acrylamide-allylamine (NIPA-AAm-AH). The These treatment methods are not practiced temperature-sensitive polymers were by conventional western medicine. They chosen as a shell for the purpose of creating can include herbal, animal derived, and a controlled drug delivery system. In this mind-body approaches to treating

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cancer.The scientific evidence about the found that lycopene inhibits the growth efficacy of these treatments either refutes of prostate cancer cells in test tubes. cancer fighting claims or is inconclusive at Lycopene also appears to reduce the the present time. risk of developing prostate cancer. Nutrition and Dietary Supplements  Vitamin E -- in one lab test, a specific A comprehensive treatment plan to support form of vitamin E blocked the growth of the health of men living with prostate prostate cancer cells. Vitamin E may cancer may include a range of also lower the risk of developing complementary and alternative therapies. prostate cancer in men who smoke. Preliminary studies suggest that some Overall, studies on vitamin E and nutritional supplements may reduce the prostate cancer have been mixed. More symptoms of some prostate cancers or research is needed to know whether reduce risk of developing it. vitamin E is helpful for men who Tips to reduce risk of developing prostate already have prostate cancer. cancer:  Eat antioxidant foods, including fruits Herbs (such as berries, watermelon, and Herbs are generally a safe way to tomatoes) and vegetables (such as strengthen and tone the body's systems. squash and bell peppers). Individuals may use herbs as dried extracts  Include more cruciferous vegetables (such as capsules, powders, and teas), (such as broccoli, cauliflower, cabbage, glycerites (glycerine extracts), or tinctures and Brussels sprouts) in diet. One (alcohol extracts). Unless otherwise preliminary study suggested men who indicated, one should make teas with 1 tsp. eat three or more servings a week herb per cup of hot water. Steep covered 5 - reduced their chance of developing 10 minutes for leaf or flowers, and 10 - 20 prostate cancer. Another study found minutes for roots. Drink 2 - 4 cups per day. that men who ate 28 or more servings  Green tea (Camellia sinensis) of all kinds of vegetables per week were standardized extract, 250 - 500 mg 35% less likely to develop prostate daily, is an antioxidant that may cancer than those who had fewer than decrease risk of cancer and heart 14 servings per week. These foods also disease. In one study, green tea extract appear to have anticancer properties in seemed to have a slight benefit in test tube studies. treating some forms of prostate cancer.  Some studies show men who regularly Use caffeine-free products. eat fish have a lower risk of prostate  Saw palmetto (Serenoarepens) cancer than those who don't eat as standardized extract, 160 mg two times much fish. daily, has been shown in some studies  High-fat diets may raise risk of prostate to help with symptoms of benign cancer. prostatic hyperplasia. It seems to have  Stay at a proper weight, and exercise anti-androgenic effects. However, it's regularly. not clear whether saw palmetto has any effect on prostate cancer. And Following nutrients may have cancer- researchers have been concerned that fighting properties saw palmetto could mask prostate  Lycopene, 15 mg two times per day, is cancer by lowering prostate-specific an antioxidant found in tomatoes and antigen (PSA) levels. However, a waterrmelon. In one preliminary study, randomized study of more than 1,000 men with prostate cancer either patients did not show this effect on PSA received a lycopene supplement or levels. placebo for 3 weeks before undergoing  Milk thistle (Silybummarianum) -- In prostate surgery. Those who received one lab test, milk thistle stopped the supplement had less aggressive prostate cancer cells from growing. growth of cancer cells than those who However, there is no evidence yet that it received placebo. Lab studies have also works in humans.

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 Pomegranate (Punicagranatum) -- In caused by prostatectomy (removal of the one study, men who had surgery or prostate). radiation to treat prostate cancer that had not spread and who drank 8 oz. of Mind-Body Medicine pomegranate juice every day slowed Meditation down the time it took their PSA levels to Meditation may reduce stress, ease anxiety, double. Researchers think that meant and allow men with prostate cancer to that their tumors may have not grown regain a sense of self-control. as fast, either. More research needs to be done. RESEARCH IN INDIA14,14a  Garlic (Allium sativum), standardized The Advanced Centre for Treatment, extract, 400 mg two to three times daily, Research and Education in Cancer may help fight cancer cells, but more (ACTREC) is actively involved in cancer research is needed to know whether it's research. effective against prostate cancer. Garlic ACTREC designed to compare Helical can interact with many medications. It Tomotherapy (HT) based IMRT and may increase the risk of bleeding, conventional sliding window (SW IMRT) in particularly if you also take blood patients with high risk prostate cancer. thinners such as warfarin (Coumadin) Complementary plans with HT and SWIMRT or aspirin. were compared using DVH parameters. The PTV Prostate was prescribed 74 Gy in 37 Acupuncture fractions and the nodal PTV received 55 Gy Acupuncture may provide relief from side in 37 fractions by simultaneous integrated effects of orchiectomy, removal of the boost. Conformity Index, Homogeneity testes. Studies also support using Index and dose-volume parameters were acupuncture to relieve pain that often compared. occurs when cancer has spread beyond the A population based case-control study on prostate, particularly to the bones. A prostate cases was carried out in Delhi to National Institutes of Health statement identify potential risk factors. Cases were released in 1997 also supports the use of each matched with two controls. Past acupuncture to reduce nausea from smoking and current alcohol consumption chemotherapy. significantly increased the risk of prostate Evidence suggests acupuncture can be a cancer. No statistically significant valuable therapy for cancer-related association was found with family history of symptoms, particularly nausea and cancer or prostate cancer. The risk of vomiting that often accompanies prostate cancer declined with increasing chemotherapy treatment. Studies have also dietary consumption of tea, citrus fruits and found that acupuncture may help reduce melon. A statistically significant marginal pain and shortness of breath. Acupressure, increase in the odds ratio was observed or pressing on rather than needling with the consumption of eggs, fish and acupuncture points, may also help control sunflower oil. Though an increased risk of breathlessness and is a technique that prostate cancer was evident among patients can learn and then use to treat vasectomised men, the association was not themselves. statistically significant.

Massage and Physical Therapy COMMERCIAL ASPECTS OF PROSTATE Studies suggest that massage reduces stress CANCER DRUGS15,15a and boosts immune function, so it may help Four new product launches in prostate relieve anxiety for men being treated for cancer over the next 10 years, including prostate cancer. Medivation’s androgen receptor inhibitor Pelvic floor exercises -- tightening and MDV3100 and Takeda’s 17, 20 lyase releasing muscles that start and stop the inhibitor TAK-700 will counter generic flow of urine -- may help with incontinence erosion. In addition Increasing use of Zytiga (abiraterone; Johnson&Johnson) and

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Jevtana (cabazitaxel;Sanofi) will boost  LHRH analogs - Zoladex, Lupron, market value from $1.7bn in 2011 to $4.3bn Eligard, Vantas, and Decapeptyl by 2020.  Antiandrogens - Casodex The report on prostate drug market from  Pipeline drugs for hormonal therapy - 2005 to 2020 covering 21 major drugs Zytiga, MDV3100, and TAK700 categorized into four therapies; namely hormonal therapy, chemotherapy, Global prostate cancer chemotherapy immunotherapy, and targeted therapy. Out drugs market - of 21 drugs, 13 are currently commercially  Off patent drugs - Taxotere, available in the market and 8 are in mitoxantrone, and Emcyt pipeline. Growing prostate cancer  Patented drugs – Jevtana. population (25% increase in the incidence of prostate cancer in mature countries and Global prostate cancer immunotherapy 40% increase in emerging countries, from drugs market- 2010 to 2020) is an impetus for the growth  Patented drug - Provenge of the market. In 2010, among the mature  Pipeline drug – ipilimumab markets, U.S. was the major contributor; accounting for 35% of the total sales of Global prostate cancer targeted therapy prostate cancer drugs and amongst the drugs market- emerging countries, China contributed to  Angiogenesis inhibitor - lanreotide, the share of about 2% of the overall TASQ, Zaltrap prostate cancer therapeutics market.  Apoptosis inducing - custirsen sodium As far as drugs are concerned, Taxotere  Signal transduction inhibitor –Sprycel accounted for 23% of the total sales of prostate cancer drugs in 2010. Astrazeneca SUMMARY AND CONCLUSION PLC is a leading market player with the The article covers the following share of 30% in the total prostate cancer a] Anatomy, Physiology & Pathophysiology therapeutics market, in 2010. However, by of Prostate gland 2020, Astrazeneca will lose its market share b] Types & Pathophysiology of prostate by 19%, due to entry of new players such as cancer Active Biotech, Bristol Myers-Squibb, Teva c] Awareness & Statistics of prostate cancer Pharmaceuticals Industries Ltd, and d] Risk factors, Prognosis ,Detection and Johnson & Johnson (entered the market in Diagnosis, Signs & Symptoms & Treatment 2011, with its key drug Zytiga). of prostate cancer Players are implementing various growth e] Drug discovery research & Recently strategies in the market to gain a discovered treatments, New dosage forms, competitive edge. New products launch, CAM therapy,& product pipelines, agreements and Commercial aspects of prostate cancer. collaborations, clinical trials, and Based on the article the following silent acquisitions were certain major strategies conclusions can be drawn : adopted by the players from January 2006 Prostate cancer survival tends to be poorer to September 2011. in developing countries, most likely because of acombination of late diagnosis and Scope of the report limited access to standard treatment. A This research report evaluates the prostate substantial proportion ofcancer burden can cancer drugs market with respect to the be prevented by implementing programs, current and pipeline drugs. The report early detection and treatment, andmajorly analyzes geography; forecasting revenue, public health check-up camps promoting and trends in each of the following investigations. Clinicians, health submarkets: professionals,and policy makers can play an active role in the application of such Global prostate cancer hormonal interventions on a pan-Indialevel. therapy drugs market - Identifying risk factors for advanced disease  LHRH antagonists - Firmagon may help to decrease the rate of poor

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prostate cancer outcomes and associated through www.ahrq.gov. [8a] mortality worldwide. National cancer institute at NIH It is recommened that every men beginning http://www.cancer.gov/cancertopic at age 50 should perform yearly PSA s/treatment/prostate/understandin screening and men who are at higher risk of g-prostate- cancer- prostate cancer, including African American treatment/page3 men and men whose father or brother had 9. Prostate Cancer Cell Line Study prostate cancer, begin screening at age 40 Shows Potential New Route to or 45. Cancer Progression, Prostate Cancer Researcher can take their research ahead Foundation (PCF) accessed through through In-Vitro evaluation using cell lines. http://www.pcf.org. [9a] Ming-Fong Lin, Technology Transfer Leader For REFERENCES The University Of Nebraska Medical 1. American Cancer Society,: Center Prostate Cancer Cellwebsite: http://cajournal.org and wwww.unemed.com http://cacancerjournal.org[1a]Natio 10. Prostrate cancer screening CDC nal Collaborating Centre for Cancer, accessed through 2008a; Burford et al, 2010; Neal, http://www.cdc.gov/cancer/prosta 2010] te/pdf/prosguide.pdf 2. Blood borne bio molecular markers 11. Support for People with Cancer, a in prostate cancer development and booklet from the National Cancer progression, Robert A. Bok & Eric J. Institute,accessed through Small. Nature Reviews Cancer 2, www.cancer.gov/publications or 1- 918-926 (December 2002). 800-4-CANCER (1-800-422- 3. Balkrishna B Yeole, Trends in the 6237).[11a] National Cancer Prostate Cancer Incidence in India, Institute’s Cancer Drug Information Asian Pacific Journal of Cancer summaries.http://www.cancer.gov/ Prevention, Vol 9, 2008. cancertopics/druginfo/prostatecanc 4. Bombay Cancer Registry, Indian er. Cancer Society, 74, JerbaiWadia 12. Xtandi Approved for Advanced Road, Bhoiwada, Parel, Mumbai – Prostate Cancer, through 400 012, Maharashtra. http://www.dddmag.com/news/20 5. Cancer Statistics, 2010, American 12/08/xtandi- approved-advanced- Cancer Society, Available online at: prostate-cancer[12a] 80 drugs in http://cajournal.org and development for prostate cancer, http://cacancerjournal.org report 6. American Cancer Society. (Accessed PhRMAhttp://prostatecancerinfolin October 2010) k.net/2011/04/06/80-drugs- in- [http://www.cancer.org/Cancer/Pr development-for-prostate-cancer- ostateCancer/DetailedGuide/prosta says-phrma [12b] Rahimi, te-cancer-risk-factors]. Maham,Magnetic Drug Targeting: 7. Murray T; Ward E ; Samuels A; Development of A Novel Drug Tiwari RC; Ghafoor A; Feuer EJ; Delivery System For Prostate Cancer Thun MJ... "Cancer statistics, 2005" . Therapy available through: website- CA Cancer J Clin 55 (1): 10–30. https://dspace.uta.edu/handle/101 doi:10.3322/canjclin.55.1.10. 06/1031[12c] Gamma-tocotrienol 8. Treatments for Localized Prostate suppresses prostate cancer cell Cancer: Systematic Review to proliferation and invasion through update the 2002 U.S. Preventive multiple-signalling pathways. Br J Services Task Force Cancer. 2008 Dec 2;99(11):1832-41 Recommendation Prepared for 13. CAM –REF Source: Agency for Healthcare Research and http://www.umm.edu/altmed/artic Quality U.S. Department of Health les/prostate-cancer- and Human Services accessed 000028.htm#ixzz2CwWMG4h0

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14. Murthy V, Mallik S, Master Z, Pac J Cancer Prev. 2010;11(2):397- Sharma PK, Mahantshetty U, 401. Shrivastava SK, Does helical 15. Market and Product Forecasts: tomotherapy improve dose Prostate Cancer conformity and normal tissue http://www.datamonitor.com/store sparing compared to conventional /Product/market_and_product_fore IMRT? A dosimetric comparison in casts_prostate_cancer. [15a] high risk prostate cancer, Technol Prostate Cancer Therapeutics Cancer Res Treat. 2011 Market (2010-2020) (Opportunity Apr;10(2):179-85.[14a] 23.Tyagi B, Analysis, Pipeline Assessment and Manoharan N, Raina VA case control Global Market Forecast) reports by study on prostate cancer in Delhi, markets and markets through, Dr. BRA Institute Rotary Cancer http://www.marketsandmarkets.co Hospital, All India Institue of m/Market-Reports/prostate- Medical Sciences, New Delhi, Asian cancer-drugs-market-413.html.

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