Cellular and Molecular Progression of Prostate Cancer: Models for Basic and Preclinical Research

Abstract

We have witnessed noteworthy progress in our understanding of prostate cancer over the past decades. This basic knowledge has been translated into efficient diagnostic and treatment approaches leading to the improvement in patient survival. However, the molecular pathogenesis of prostate cancer appears to be complex, and histological findings often do not provide an accurate assessment of disease aggressiveness and future course. Moreover, we also witness tremendous racial disparity in prostate cancer incidence and clinical outcomes necessitating a deeper understanding of molecular and mechanistic bases of prostate cancer. Biological research heavily relies on model systems that can be easily manipulated and tested under a controlled experimental environment. Over the years, several cancer cell lines have been developed representing diverse molecular subtypes of prostate cancer. In addition, several animal models have been developed to demonstrate the etiological molecular basis of the prostate cancer. In recent years, patient-derived xenograft and 3-D culture models have also been created and utilized in preclinical research. This review is an attempt to succinctly discuss existing information on the cellular and molecular progression of prostate cancer. We also discuss available model systems and their tested and potential utility in basic and preclinical prostate cancer research.

Establishment and Characterization of Patient-Derived Xenografts (PDXs) of Different Histology from Malignant Pleural Mesothelioma Patients

“…We demonstrated that the in vitro response in cells growing in monolayer does not always reflect the situation in more complex systems. The strong differential activity of olaparib in 3D vs. 2D growing cells was particularly intriguing, and was not in agreement with the finding obtained with other cellular systems and other drugs [ 34 , 35 , 36 , 37 , 38 ]. Olaparib, a drug currently under investigation in different solid tumors [ 39 , 40 , 41 , 42 , 43 ], is a potential candidate for MPM due to the reported mutations in the BRCA1-associated protein (BAP-1) gene found in MPM.…”

Metformin and Androgen Receptor-Axis-Targeted (ARAT) Agents Induce Two PARP-1-Dependent Cell Death Pathways in Androgen-Sensitive Human Prostate Cancer Cells

“…Given the long doubling times of the LNCaP and VCaP cell populations (42 to 51 h; Figure S1) [34], the effects of the agents of interest (Abi, Enz, metformin, and ARAT + metformin combinations) on cell proliferation become apparent only after the longer incubation times. For instance, compared to controls, the anti-proliferative effects of the above treatments on LNCaP cells are observed at day 3 or beyond after the drug treatments ( Figure S1).…”

Inhibition of Scavenger Receptor Class B Type 1 (SR-B1) Expression and Activity as a Potential Novel Target to Disrupt Cholesterol Availability in Castration-Resistant Prostate Cancer

“…Cholesterol is the essential precursor of steroid synthesis, including androgens [ 41 ]. AR signaling drives PCa and plays an essential role in the development and progression of the disease [ 42 , 43 , 44 , 45 , 46 , 47 ]. As an essential component in cell membranes [ 48 ], and a mediator of cell proliferation and inflammatory pathways [ 41 , 49 ], there are multiple ways cholesterol needs can be exploited to target PCa pathophysiology.…”