Let’s Go 3D! New Generation of Models for Evaluating Drug Response and Resistance in Prostate Cancer

Abstract

Prostate cancer (PC) is the third most frequently diagnosed cancer worldwide and the second most frequent in men. Several risk factors can contribute to the development of PC, and those include age, family history, and specific genetic mutations. So far, drug testing in PC, as well as in cancer research in general, has been performed on 2D cell cultures. This is mainly because of the vast benefits these models provide, including simplicity and cost effectiveness. However, it is now known that these models are exposed to much higher stiffness; lose physiological extracellular matrix on artificial plastic surfaces; and show changes in differentiation, polarization, and cell–cell communication. This leads to the loss of crucial cellular signaling pathways and changes in cell responses to stimuli when compared to in vivo conditions. Here, we emphasize the importance of a diverse collection of 3D PC models and their benefits over 2D models in drug discovery and screening from the studies done so far, outlining their benefits and limitations. We highlight the differences between the diverse types of 3D models, with the focus on tumor–stroma interactions, cell populations, and extracellular matrix composition, and we summarize various standard and novel therapies tested on 3D models of PC for the purpose of raising awareness of the possibilities for a personalized approach in PC therapy.

A Marine Collagen-Based 3D Scaffold for In Vitro Modeling of Human Prostate Cancer Niche and Anti-Cancer Therapeutic Discovery

“…Therefore, switching from 2D cultures and animal models to 3D in vitro cell culture is emerging as a crucial technique in cancer research, thereby enhancing the understanding of the biological mechanisms underlying cancer progression, such as drug resistance and metastasis, as well as facilitating the identification of biomarkers and development of therapeutic strategies [46]. Despite extensive research on 3D in vitro PC models to replicate cancer complexity [47][48][49][50][51], no definitive and ideal model has yet been established, and ongoing detailed studies continue to reveal new and intriguing information.…”

Radiobiological Assessment of Targeted Radionuclide Therapy with [177Lu]Lu-PSMA-I&T in 2D vs. 3D Cell Culture Models

“…Multicellular tumor spheroids can enhance the predictive power and minimize the error by being a better mimic, ultimately reducing time and costs during drug development by the earlier detection of ineffective agents [23]. Thus, 3D models are credited to be fundamental tools in pharmaceutical development and biomedical research in the future [23,24].…”

Applications of Tumor Cells in an In Vitro 3D Environment

“…Various clinical PCa models have been developed to clarify the complex underlying mechanisms regarding the treatment resistance of PCa [74,75]. The existing in vitro 3D cell culture methods for PCa cells have been reviewed, with advantages and disadvantages discussed [17,75].…”

“…Various clinical PCa models have been developed to clarify the complex underlying mechanisms regarding the treatment resistance of PCa [74,75]. The existing in vitro 3D cell culture methods for PCa cells have been reviewed, with advantages and disadvantages discussed [17,75]. The 3D cell culture methods of PCa include suspension cell cultures, hanging drop methods, microfluidic devices, gel-embedded scaffolds, and patient-derived xenografts or explants.…”

“…Petric et al discussed the development of organoid cultures of PCa tumor cells [75]. The origin of the organ-specific cells is often stem cells or progenitor cells.…”