# Applications of Tumor Cells in an _In Vitro_ 3D Environment
## 7 Applications of 3D Models of Cancer Cells
### Prostate Cancer  
Prostate cancer (PCa) is the second most frequent malignancy in men and accounts for about one-fourth of all cancer cases amongst them worldwide [47]. Even though it is not the most fatal cancer type and its course is often indolent, the mortality rate is still relatively high, and every fourth PCa patient eventually dies. The occurrence and mortality rates of PCa exhibit a significant correlation with factors such as high age, ethnicity, or race, as well as environmental and geographic variables [64; 65]. PCa develops from normal prostate epithelium through a multistep histological transformation process governed by various underlying molecular changes [66; 67]. Most patients can benefit from treatment at an early stage through a reduction in tumor volume and a rapid decrease in prostate-specific antigens (PSAs) [68]. PSA screening and its enhancements have long been considered \"the golden standard\" in PCa detection and have significantly lowered the PCa mortality rate. Despite the controversy caused by the US Preventive Services Task Force reports in 2008 and 2012 referring to overdiagnosis of insignificant cancers and unnecessary prostate biopsies, it still has an important role in PCa screening and early detection [69]. Novel biomarkersfound in both serum and urine, along with their various combinations, are becoming prevalent and have been extensively reviewed [70]. Androgen deprivation therapy (ADT) is an effective therapeutic strategy for PCa. Since androgens have important roles in the body, their deprivation, especially in terms of continuous ADT, can lead to numerous unfavorable effects, such as cardiovascular maladies, bone density loss, metabolic changes, sexual dysfunction, hot flushes, and, last but not least, adverse psychological reactions [71]. Despite the initial response to ADT, patients develop castration resistance, leading to recurrence and/or castration-resistant PCa [72]. Moreover, metastatic PCa that progresses after castration resistance remains incurable [73]. 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. As for all tumor types investigated, cell lines are widely used in _in vitro_ 3D cell culture methods. The three classic PCa cell lines, DU145, PC-3, and LNCaP, are from clinical metastatic lesions and the most widely used cell lines in PCa research [74]. At present, several PCa cell lines have been established from primary PCa tumors, PCa metastases, and PCa xenograft models. In addition, many sublines have been developed from these three classic PCa cell lines, especially the LNCaP cell line [74]. The parental LNCaP cells are androgen-sensitive, but sublines of these cells, such as LNCaP-abl and LNCaP-LTAD, are androgen-insensitive due to their establishment through the depletion of androgen in culture media. However, the utilization of cell lines comes with limitations due to their lack of resemblance to the tumors of origin [76]. [PERSON] 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. Together with a scaffolding ECM, they often grow to resemble the original tumor, both in structure and function [77]. Moreover, advantages with organoids include the ability to keep them in long-term culture, perform genetic manipulations, and cryopresherem them [75, 78]. Of importance is also maintaining the TME _in vitro_ with the addition of supporting cells, such as CAFs, immune cells, and endothelial cells. Several examples of the successful establishment of organoids from patient biopsies have been discussed by [PERSON] et al. [66].