Use of conditional reprogramming cell, patient derived xenograft and organoid for drug screening for individualized prostate cancer therapy: Current and future perspectives (Review).

Abstract

Prostate cancer mortality is ranked second among all cancer mortalities in men worldwide. There is a great need for a method of efficient drug screening for precision therapy, especially for patients with existing drug‑resistant prostate cancer. Based on the concept of bacterial cell culture and drug sensitivity testing, the traditional approach of cancer drug screening is inadequate. The current and more innovative use of cancer cell culture and invivo tumor models in drug screening for potential individualization of anti‑cancer therapy is reviewed and discussed in the present review. An ideal screening model would have the ability to identify drug activity for the targeted cells resembling what would have occurred in the invivo environment. Based on this principle, three available cell culture/tumor screening models for prostate cancer are reviewed and considered. The culture conditions, advantages and disadvantages for each model together with ideas to best utilize these models are discussed. The first screening model uses conditional reprogramed cells derived from patient cancer cells. Although these cells are convenient to grow and use, they are likely to have different markers and characteristics from original tumor cells and thus not likely to be informative. The second model employs patient derived xenograft (PDX) which resembles an invivo approach, but its main disadvantages are that it cannot be easily genetically modified and it is not suitable for high‑throughput drug screening. Finally, high‑throughput screening is more feasible with tumor organoids grown from patient cancer cells. The last system still needs a large number of tumor cells. It lacks insitu blood vessels, immune cells and the extracellular matrix. Based on these current models, future establishment of an organoid data bank would allow the selection of a specific organoid resembling that of an individual's prostate cancer and used for screening of suitable anticancer drugs. This can be further confirmed using the PDX model. Thus, this combined organoid‑PDX approach is expected to be able to provide the drug sensitivity testing approach for individualization of prostate cancer therapy in the near future.