Cancer Stem Cells in Prostate Cancer: Implications for Targeted Therapy

Abstract

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and the second most common cause of cancer-related mortality among men in the developed world. Conventional anti-PCa therapies include surgery, radiation, hormonal ablation, and chemotherapy. Despite increasing efforts, these therapies are not effective for patients with advanced and/or metastatic disease. In most cases, cancer therapies fail due to an incomplete depletion of tumor cells, resulting in tumor relapse. The cancer stem cell (CSC) hypothesis is an emerging model that explains many of the molecular characteristics of oncological disease as well as the tendency of cancers to relapse, metastasize, and develop resistance to conventional therapies. CSCs are a reservoir of cancer cells that exhibit properties of self-renewal and the ability to reestablish the heterogeneous tumor cell population. The existence of PCa stem cells offers a theoretical explanation for many uncertainties regarding PCa and also for treatment resistance and disease progression once clinical cure is achieved. Therapies targeting CSCs might therefore lead to more effective cancer treatments, divergent from a traditional anti-proliferative approach, based on tumor bulk reduction accompanied by CSC-specific inhibition. Here, we focus on reviewing the historical perspective as well as concepts regarding stem cells and CSCs in PCa. In addition, we will report possible strategies and new clinical approaches that address the CSC-based concept of tumorigenesis in PCa.

THBS4 silencing regulates the cancer stem cell‐like properties in prostate cancer via blocking the PI3K/Akt pathway

“…PCa stem cells occupy only a small proportion of the tumor mass but are characterized by strengthened clonogenicity as well as therapeutic resistance 18 . The presence of PCa stem cells provides a theoretical explanation for the consequence of uncertainties regarding PCa, therapeutic resistance along with cancer progression once the disease is clinically cured 19 . CD133 + phenotype was a novel marker for human cancer stem cells, and CD133 + cells exhibit high migration, invasion, and colony‐forming ability 20 .…”

Role of miRNA-Regulated Cancer Stem Cells in the Pathogenesis of Human Malignancies

“…PCa development is a complex and heterogenous phenomenon, and the available therapeutic options such given radiation therapy, hormonal therapy, or chemotherapy are not promising in the patients with advanced and/or metastatic disease and are associated with various complications. Increasing evidences revealed that the presence of CSCs in prostate cancer tissue is one of the sole reasons for the available therapeutic clinical failure as they play a critical role in self-renewal, epithelial-mesenchymal transition, metastasis, and drug resistance [159]. The role of miRNAs in the PCa heterogeneity and aggressiveness is very well elucidated in various preclinical and clinical reports carried out throughout the world.…”

Enhanced targeting of prostate cancer‑initiating cells by salinomycin‑encapsulated lipid‑PLGA nanoparticles linked with CD44 antibodies

“…This can be attributed to metastasis, drug resistance and high rates of recurrence (3,4). One of the main causes for these phenomena is the persistence of prostate cancer-initiating cells (CICs) (5)(6)(7). Therefore, the elimination of prostate CICs may contribute significantly towards treatment strategies for prostate cancer.…”