Mechanisms of Prostate Cancer Cells Survival and Their Therapeutic Targeting

Abstract

Prostate cancer (PCa) is today the second most common cancer in the world, with almost 400,000 deaths annually. Multiple factors are involved in the etiology of PCa, such as older age, genetic mutations, ethnicity, diet, or inflammation. Modern treatment of PCa involves radical surgical treatment or radiation therapy in the stages when the tumor is limited to the prostate. When metastases develop, the standard procedure is androgen deprivation therapy, which aims to reduce the level of circulating testosterone, which is achieved by surgical or medical castration. However, when the level of testosterone decreases to the castration level, the tumor cells adapt to the new conditions through different mechanisms, which enable their unhindered growth and survival, despite the therapy. New knowledge about the biology of the so-called of castration-resistant PCa and the way it adapts to therapy will enable the development of new drugs, whose goal is to prolong the survival of patients with this stage of the disease, which will be discussed in this review.

Keywords: antiandrogen resistance; cancer; new drugs; prostate; therapy.

Figure 1

Stroma–epithelium interaction. E2 = estradiol; T = testosterone; 5α-DHT = 5α- dihydrotestosterone; GF = growth factor; SF = survival factor; PSA = prostate specific antigen; hK2 = human glandular kallikrein; BC = basal cell, SC = secretory cell. (Drawing: Pejčić T.).

Figure 2

Incidence and mortality rates by age group for PCa in 2020. Source: GLOBOCAN 2020.