Recent advances and future perspectives in the therapeutics of prostate cancer

Abstract

Prostate cancer (PC) is one of the most common cancers in males and the fifth leading reason of death. Age, ethnicity, family history, and genetic defects are major factors that determine the aggressiveness and lethality of PC. The African population is at the highest risk of developing high-grade PC. It can be challenging to distinguish between low-risk and high-risk patients due to the slow progression of PC. Prostate-specific antigen (PSA) is a revolutionary discovery for the identification of PC. However, it has led to an increase in over diagnosis and over treatment of PC in the past few decades. Even if modifications are made to the standard PSA testing, the specificity has not been found to be significant. Our understanding of PC genetics and proteomics has improved due to advances in different fields. New serum, urine, and tissue biomarkers, such as PC antigen 3 (PCA3), have led to various new diagnostic tests, such as the prostate health index, 4K score, and PCA3. These tests significantly reduce the number of unnecessary and repeat biopsies performed. Chemotherapy, radiotherapy, and prostatectomy are standard treatment options. However, newer novel hormone therapy drugs with a better response have been identified. Androgen deprivation and hormonal therapy are evolving as new and better options for managing hormone-sensitive and castration-resistant PC. This review aimed to highlight and discuss epidemiology, various risk factors, and developments in PC diagnosis and treatment regimens.

Keywords: Diagnosis; Prostate cancer; Quality of life; Risk factors; Treatment.

Fig. 1

Timeline demonstrating evolution in the treatment regimen for PC

Fig. 2

Mechanism of action of Taxanes: a Taxane derivatives bind to β tubulin which leads to microtubule stabilization, this inhibits the proper assembly of microtubules and inhibits G2-M transition and apoptosis. b Taxanes are able to inhibit AR activity by FOXO1 mediated inhibition of AR transcriptional activity. c Taxanes inhibit antiapoptotic proteins (BCL2, and BCL-XL) and promotes activation of proapoptotic proteins (BAX, and BAK) leads to the release of cytochrome c that activates intrinsic apoptotic pathway, which leads to cell death (AR: Androgen Receptor and ARE: Androgen Receptor Element)

Fig. 3

Mechanism of action of Abiraterone acetate and Enzalutamide. Abiraterone acetate inhibits the synthesis of androgen by blocking the action of 17α-hydroxylase and C 17, 20-lyase on CYP-17, leading to the inhibition in binding of testosterone to AR. Enzalutamide binds with AR and inhibits the binding of testosterone to AR. It also inhibits nuclear translocation of AR (AA: Abiraterone acetate, E: Enzalutamide, ARE: Androgen Receptor Element, AR: Androgen Receptor, T: testosterone, DHEA: Dehydroepiandrosterone)

Fig. 4

Mechanism of action of Sipuleucel-T. Sipuleucel-T is an autologous cellular immunological agent, here blood cells from prostate cancer patients are taken and processed through leukapheresis then density gradient centrifugation of leukocytes is done to get monocytes, monocytes are fused with fusion protein (PAP and GM-CSF) then it is culture for 36–44 h, infused monocyte is intravenously administered back to the patient. Infused monocyte having GM-CSF activates the APC that led to prostate tumor cell lysis by CD8 T cell. (GM-CSF-Granulocyte macrophage colony-stimulating factor, PAP-Prostatic acid phosphatase, APC- Antigen presenting cells)