Prostate Cancer Organoids for Tumor Modeling and Drug Screening.

Prostate cancer (PCa) is the second most common malignancy and the fifth leading cause of cancer death in men worldwide. Despite its prevalence, the highly heterogenic PCa has shown difficulty to establish representative cell lines that reflect the diverse phenotypes and different stages of the disease in vitro and hence hard to model in preclinical research. The patient-derived organoid (PDO) technique has emerged as a groundbreaking three-dimensional (3D) tumor modeling platform in cancer research. This versatile assay relies on the unique ability of cancer stem cells (CSCs) to self-organize and differentiate into organ-like mini structures. The PDO culture system allows for the long-term maintenance of cancer cells derived from patient tumor tissues. Moreover, it recapitulates the parental tumor features and serves as a superior preclinical model for in vitro tumor representation and personalized drug screening. Henceforth, PDOs hold great promise in precision medicine for cancer. Herein, we describe the detailed protocol to establish and propagate organoids derived from isolated cell suspensions of PCa patient tissues or cell lines using the 3D semisolid Matrigel™-based hanging-drop method. In addition, we highlight the relevance of PDOs as a tool for evaluating drug efficacy and predicting tumor response in PCa patients.

MicroRNAs as clinical tools for diagnosis, prognosis, and therapy in prostate cancer.

Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men worldwide. Despite the presence of accumulated clinical strategies for PCa management, limited prognostic/sensitive biomarkers are available to follow up on disease occurrence and progression. MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression through post-transcriptional regulation of their complementary target messenger RNA (mRNA). MiRNAs modulate fundamental biological processes and play crucial roles in the pathology of various diseases, including PCa. Multiple evidence proved an aberrant miRNA expression profile in PCa, which is actively involved in the carcinogenic process. The robust and pleiotropic impact of miRNAs on PCa suggests them as potential candidates to help more understand the molecular landscape of the disease, which is likely to provide tools for early diagnosis and prognosis as well as additional therapeutic strategies to manage prostate tumors. Here, we emphasize the most consistently reported dysregulated miRNAs and highlight the contribution of their altered downstream targets with PCa hallmarks. Also, we report the potential effectiveness of using miRNAs as diagnostic/prognostic biomarkers in PCa and the high-throughput profiling technologies that are being used in their detection. Another key aspect to be discussed in this review is the promising implication of miRNAs molecules as therapeutic tools and targets for fighting PCa.

Drug resistance in metastatic castration-resistant prostate cancer: an update on the status quo.

Prostate cancer (PCa) is a leading cause of cancer-related morbidity and mortality in men globally. Despite improvements in the diagnosis and treatment of PCa, a significant proportion of patients with high-risk localized disease and all patients with advanced disease at diagnosis will experience progression to metastatic castration-resistant prostate cancer (mCRPC). Multiple drugs are now approved as the standard of care treatments for patients with mCRPC that have been shown to prolong survival. Although the majority of patients will respond initially, primary and secondary resistance to these therapies make mCRPC an incurable disease. Several molecular mechanisms underlie the development of mCRPC, with the androgen receptor (AR) axis being the main driver as well as the key drug target. Understanding resistance mechanisms is crucial for discovering novel therapeutic strategies to delay or reverse the progression of the disease. In this review, we address the diverse mechanisms of drug resistance in mCRPC. In addition, we shed light on emerging targeted therapies currently being tested in clinical trials with promising potential to overcome mCRPC-drug resistance.