**Abstract**

Prostate cancer is one of the leading cancers in men needs a long period for development from small lesion to become a clinical manifestation. The prostate specific antigen is a prominent tumor marker for prostate cancer. Androgens are involved in the development and progression of prostate cancer regulating the androgen receptor as androgen-dependent or androgen-independent types. The latter occurs in metastatic conditions of prostate cancer developed as hormone resistant prostate cancer (HRPC) that inappropriately activates transcription of other genes involved in molecular pathways inducing cellular proliferation and inhibiting apoptosis. Since prostate cancer is characterized by slow growth and long latency period and thus integration of phytochemicals/compounds in combination with other existing therapies have promising future to manage cancer, thus controlling the disease progression and mortality rate. Therefore, the medicinal plants therapeutic or prophylactic activities on prostate cancer exhibiting anti-androgenic effects, depleting PSA, down-regulating expression of androgen receptor, regulating cell cycle regulators have promising future to be applied as adjuvant drugs in prostate cancer treatment.

**Keywords:** prostate cancer, androgen receptor, PSA, systemic therapy, phytochemicals, molecular pathways

## **1. Introduction**

Statistical reports revealed that prostate cancer is the third leading cause of cancer deaths in men [1] causing the life of one in every 39 men in United States. Related to prostate cancer rates in India, the rates are more than 20 times higher in US whites, more than 10 times higher in US Asian Indians/Pakistanis, seven times higher among UK South Asians and twice as high among Singapore Indians [2]. Factors escalating the risk of prostate cancer include age above 50 years, cancer incidence in family, ethnicity, modern diet, environmental factor, pollutants, etc. The role of inflammation in prostate diseases is suggested by the presence of inflammatory cells within the prostate of cancer patients [3]. The molecular mechanism responsible for inflammation mediated prostate cancer is not yet clear.

However, prostate cancer needs a long period for development from small lesion to become a clinical manifestation [4]. Tumor progression is revealed with complications in erectile dysfunction, skeletal bone pain, obstruction of lymph vessels,

and veins causing lower body edema. The development of high-grade prostatic intraepithelial neoplasia (HGPIN) is identified as an intermediate stage between benign epithelium and the invasive malignant carcinoma at the outset of prostate cancer. Four main patterns of high-grade PIN (HGPIN) have been described as tufting, micropapillary, cribriform, and flat [5].

Prostate specific antigen (PSA), major constituent in prostatic secretion and is used for screening prostatism. PSA testing is primarily associated with benign prostatic hyperplasia (BPH), however there is only rare connectivity of patients having BPH to develop prostate cancer. With conditions like BPH, inflammation, and disruption of prostate basal membrane increases the permeability and releases PSA into the circulation. Prostate cancer antigen 3 (PCA3) is more specific than PSA which is an important biomarker in personalized medicine. Also analysis of urinary protein markers, such as TMPRSS2-ERG and PCA3 are helpful in early diagnosis of the disease. The other tumors markers reported as prostatic acid phosphatase (PAP), cytoskeletal proteins, and annexin I are downregulated in PIN whereas C-erbB-2 (HER-2/neu) and C-erbB-3 oncoproteins, c-met protooncogene, Bcl-2 oncoprotein, several growth factors, nitric oxide synthase, alpha-methylacyl-CoA racemase, glycoprotein A-80, and apolipoprotein D, are upregulated in PIN. The histological grading system of prostate cancer is obtained from the Gleason score [6] which provides information that score 1–5 indicates low-grade prostate cancer and score 8–10 indicates high-grade prostate cancer. Digital rectal examination (DRE), examination of PSA levels, prostate ultrasound, and prostate biopsy are the current diagnostic methods in examining the primary and metastatic stages for prostate cancer [7, 8]. Prostate cancer stages are generally classified into three categories—T category, N category, and M category. T represents the primary tumor, N represents the cancer that has spread to regional (nearby) lymph nodes and M represents the distant metastasis cancer. The treatment strategies are administered based on the stage of cancer progression.
