Precision Medicine In Prostate Cancer Research Articles

Ultrasensitive detection of PSA in human serum using Label-Free electrochemical biosensor with magnetically induced Self-Assembly based on α-Fe2O3/Fe3O4@Au nanocomposites

To achieve the goals of early diagnosis, screening, and precision medicine for prostate cancer, this research designed a label-free electrochemical biosensor by combining magnetic probes (PSAA/α-Fe2O3/Fe3O4@Au) with magnetically induced self-assembly (MISA) technology to explore the application of prostate-specific antigen (PSA) in precise detection. Magnetic α-Fe2O3/Fe3O4 nanoparticles (NPs) were constructed using a hydrothermal-calcination reduction method. Subsequently, α-Fe2O3/Fe3O4@Au nanocomposites were prepared by reducing HAuCl4 with NaBH4 at a low temperature. The self-assembly method was adopted in two steps: firstly, the sulfhydryl-modified PSA aptamer is immobilized onto the material surface using Au–S bonds; secondly, the magnetic NPs and magnetic glassy carbon electrode (MGCE) undergo self-assembly. The biosensor showed good linear response in the range of 100 fg/mL to 100 ng/mL, with a detection limit of 0.78 pg/mL (S/N = 3) under optimal conditions. Repeatability, stability, selectivity, reproducibility, and the capability to analyze real samples were also investigated. With its cost-effectiveness, operational simplicity, and speed of analysis, the biosensing system platform holds great potential as a valuable tool in clinical PSA detection for point-of-care testing (POCT).

A new tumorgraft panel to accelerate precision medicine in prostate cancer.

Despite the significant advances in the management of advanced prostate cancer (PCa), metastatic PCa is currently considered incurable. For further investigations in precision treatment, the development of preclinical models representing the complex prostate tumor heterogeneity are mandatory. Accordingly, we aimed to establish a resource of patient-derived xenograft (PDX) models that exemplify each phase of this multistage disease for accurate and rapid evaluation of candidate therapies. Fresh tumor samples along with normal corresponding tissues were obtained directly from patients at surgery. To ensure that the established models reproduce the main features of patient's tumor, both PDX tumors at multiple passages and patient's primary tumors, were processed for histological characteristics. STR profile analyses were also performed to confirm patient identity. Finally, the responses of the PDX models to androgen deprivation, PARP inhibitors and chemotherapy were also evaluated. In this study, we described the development and characterization of 5 new PDX models of PCa. Within this collection, hormone-naïve, androgen-sensitive and castration-resistant (CRPC) primary tumors as well as prostate carcinoma with neuroendocrine differentiation (CRPC-NE) were represented. Interestingly, the comprehensive genomic characterization of the models identified recurrent cancer driver alterations in androgen signaling, DNA repair and PI3K, among others. Results were supported by expression patterns highlighting new potential targets among gene drivers and the metabolic pathway. In addition, in vivo results showed heterogeneity of response to androgen deprivation and chemotherapy, like the responses of patients to these treatments. Importantly, the neuroendocrine model has been shown to be responsive to PARP inhibitor. We have developed a biobank of 5 PDX models from hormone-naïve, androgen-sensitive to CRPC primary tumors and CRPC-NE. Increased copy-number alterations and accumulation of mutations within cancer driver genes as well as the metabolism shift are consistent with the increased resistance mechanisms to treatment. The pharmacological characterization suggested that the CRPC-NE could benefit from the PARP inhibitor treatment. Given the difficulties in developing such models, this relevant panel of PDX models of PCa will provide the scientific community with an additional resource for the further development of PDAC research.

Omics sciences and precision medicine in prostate cancer.

In the last decade, Prostate Cancer (PCa) has emerged as the second most prevalent and serious medical condition, and is considered one of the leading factors contributing to global mortality rates. Several factors (genetic as well as environmental) contribute to its development and seriousness. Since the disease is usually asymptomatic at early stages, it is typically misdiagnosed or over-diagnosed by the diagnostic procedures currently in use, leading to improper treatment. Effective biomarkers and diagnostic techniques are desperately needed in clinical settings for better management of PCa patients. Studies integrating omics sciences have shown that the accuracy and dependability of diagnostic and prognostic evaluations have increased because of the use of omics data; also, the treatment plans using omics can be facilitated by personalized medicine. The present review emphasizes innovative multi-omics methodologies, encompassing proteomics, genomics, microbiomics, metabolomics, and transcriptomics, with the aim of comprehending the molecular alterations that trigger and contribute to PCa. The review shows how early genomic and transcriptomic research has made it possible to identify PCa-related genes that are controlled by tumor-relevant signaling pathways. Proteomic and metabolomic analyses have recently been integrated, advancing our understanding of the complex mechanisms at play, the multiple levels of regulation, and how they interact. By applying the omics approach, new vulnerabilities may be discovered, and customized treatments with improved efficacy will soon be accessible.

Clinical Application of Poly(ADP-ribose) Polymerase (PARP) Inhibitors in Prostate Cancer.

Approximately a quarter of men with metastatic castrate resistant prostate cancer (mCRPC) have alterations in homologous recombination repair (HRR). These patients exhibit enhanced sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Leveraging the synthetic lethality between PARP inhibition and HRR deficiency, studies have established marked clinical benefit and a survival advantage from PARP inhibitors (PARPi) in mCRPC, most notably in cancers with BRCA1/2 alterations. The role of PARPi is evolving beyond patients with HRR alterations, with studies increasingly focused on exploiting synergistic effects from combination therapeutics. Strategies combining PARP inhibitors with androgen receptor pathway inhibitors, radiation, radioligand therapy, chemotherapy and immunotherapy demonstrate potential additional benefits in mCRPC and these approaches are rapidly moving into the metastatic hormone sensitive treatment paradigm. In this review we summarise the development and expanding role of PARPi in prostate cancer including biomarkers of response, the relationship between the androgen receptor and PARP, evidence for combination therapeutics and the future directions of PARPi in precision medicine for prostate cancer.

Germline mutations in prostate cancer: a systematic review of the evidence for personalized medicine.

The goal of precision medicine in prostate cancer (PCa) is to individualize the treatment according to the patient's germline mutation status. PCa has a very high rate of genetic predisposition compared with other cancers in men, with an estimated rate of cancers ascribable to hereditary factors of 5-15%. A systematic search (PubMed, Web of Science, and ClinicalTrials.gov) of English literature from 2000 to 2022, using the keywords "prostate cancer", "germline mutations", "family history", and "inheritance" was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The search identified 980 publications. Of these, 200 papers were removed before screening (duplicates, non-English literature, and publication year before 2000) and 245 records were excluded after title/abstract screening. Finally, 50 articles were included in the final analysis. We analyze the latest evidence on the genetic basis of PCa predisposition and clinical implications for more personalized screening protocols and therapeutic management of this high-prevalent cancer. Emerging data show that germline mutations in homologous recombination genes (BRCA1/2, ATM, CHECK2), in mismatch repair genes (MLH1, MLH2, MSH6), and other additional genes are associated with the development and aggressiveness of PCa. Germline testing and genetic counseling have increasingly important implications in cancer screening and therapeutic decisions making for patients affected by PCa. Patients with localized PCa and some gene mutations are more likely to develop aggressive cancer, so active treatment may be preferable to active surveillance for these patients. Moreover, in patients with metastatic PCa, these gene alterations may be useful biomarkers for predicting response to specific therapy such as PARP inhibitors, recently approved for the treatment of metastatic castration-resistant PCa. The evidence supports recent guidelines and recommendations considering germline genetic testing for patients with a positive family history of PCa or men with high risk or metastatic disease.

Androgen receptor mutations for precision medicine in prostate cancer

Hormonal therapies including androgen deprivation therapy and androgen receptor (AR) pathway inhibitors such as abiraterone and enzalutamide have been widely used to treat advanced prostate cancer. However, treatment resistance emerges after hormonal manipulation in most prostate cancers, and it is attributable to a number of mechanisms, including AR amplification and overexpression, AR mutations, the expression of constitutively active AR variants, intra-tumor androgen synthesis, and promiscuous AR activation by other factors. Although various AR mutations have been reported in prostate cancer, specific AR mutations (L702H, W742L/C, H875Y, F877L, and T878A/S) were frequently identified after treatment resistance emerged. Intriguingly, these hot spot mutations were also revealed to change the binding affinity of ligands including steroids and antiandrogens and potentially result in altered responses to AR pathway inhibitors. Currently, precision medicine utilizing genetic and genomic data to choose suitable treatment for the patient is becoming to play an increasingly important role in clinical practice for prostate cancer management. Since clinical data between AR mutations and the efficacy of AR pathway inhibitors are accumulating, monitoring the AR mutation status is a promising approach for providing precision medicine in prostate cancer, which would be implemented through the development of clinically available testing modalities for AR mutations using liquid biopsy. However, there are few reviews on clinical significance of AR hot spot mutations in prostate cancer. Then, this review summarized the clinical landscape of AR mutations and discussed their potential implication for clinical utilization.

Precision Medicine for Prostate Cancer Based on Genetic Mutation

Precision Medicine for Prostate Cancer Based on Genetic Mutation

Characterization of Immune-Based Molecular Subtypes and Prognostic Model in Prostate Adenocarcinoma.

Prostate adenocarcinoma (PRAD), also named prostate cancer, the most common visceral malignancy, is diagnosed in male individuals. Herein, in order to obtain immune-based subtypes, we performed an integrative analysis to characterize molecular subtypes based on immune-related genes, and further discuss the potential features and differences between identified subtypes. Simultaneously, we also construct an immune-based risk model to assess cancer prognosis. Our findings showed that the two subtypes, C1 and C2, could be characterized, and the two subtypes showed different characteristics that could clearly describe the heterogeneity of immune microenvironments. The C2 subtype presented a better survival rate than that in the C1 subtype. Further, we constructed an immune-based prognostic model based on four screened abnormally expressed genes, and they were selected as predictors of the robust prognostic model (AUC = 0.968). Our studies provide reference for characterization of molecular subtypes and immunotherapeutic agents against prostate cancer, and the developed robust and useful immune-based prognostic model can contribute to cancer prognosis and provide reference for the individualized treatment plan and health resource utilization. These findings further promote the development and application of precision medicine in prostate cancer.

Future directions for precision oncology in prostate cancer.

Clinical genomic testing is becoming routine in prostate cancer, as biomarker-driven therapies such as poly-ADP ribose polymerase (PARP) inhibitors and anti-PD1 immunotherapy are now approved for select men with castration-resistant prostate cancer harboring alterations in DNA repair genes. Challenges for precision medicine in prostate cancer include an overall low prevalence of actionable genomic alterationsand a still limited understanding of the impact of tumor heterogeneity and co-occurring alterations on treatment response and outcomes across diverse patient populations. Expanded tissue-based technologies such as whole-genome sequencing, transcriptome analysis, epigenetic analysis, and single-cell RNA sequencing have not yet entered the clinical realm and could potentially improve upon our understanding of how molecular features of tumors, intratumoral heterogeneity, and the tumor microenvironment impact therapy response and resistance. Blood-based technologies including cell-free DNA, circulating tumor cells (CTCs), and extracellular vesicles (EVs) are less invasive molecular profiling resources that could also help capture intraindividual tumor heterogeneity and track dynamic changes that occur in the context of specific therapies. Furthermore, molecular imaging is an important biomarker tool within the framework of prostate cancer precision medicine with a capability to detect heterogeneity across metastases and potential therapeutic targets less invasively. Here, we review recent technological advances that may help promote the future implementation and value of precision oncology testing for patients with advanced prostate cancer.

Biomarker-driven immunotherapy for precision medicine in prostate cancer.

Although immunotherapy has recently revolutionized standard of care in different cancer types, prostate cancer has generally failed to show dramatic responses to immune checkpoint inhibitors. As in other tumors, the goal in prostate cancer is now to target treatments more precisely on patient's individual characteristics through precision medicine. Defects in mismatch repair, mutations in the exonuclease domain of the DNA polymerase epsilon (POLE), high tumor mutational burden and the presence of biallelic loss of CDK12 among others, are predictive biomarkers of response to immunotherapy. In the present review, we summarize the evolving landscape of immunotherapy in prostate cancer, including precision approaches and strategies to define classes of responsive patients and scale up resistance to immune checkpoint inhibitors.

Abstract CC07-01: Whole exome and whole genome methylation sequencing of low-input cfDNA to implement precision medicine in metastatic castration resistant prostate cancer

Abstract Purpose Liquid biopsy has become increasingly important in cancer diagnosis, personalized medicine, and disease progression monitoring. Conventional liquid biopsy relies on targeted cancer gene panels which often contain fewer than 500 genes. Despite the revolutionary impact of liquid biopsy on cancer research and patient care, targeted gene panels may miss key novel mutations involved in cancer development and drug response, and other novel genomic alternations underlining cancer development, such as whole genome structural or epigenetic changes. Additionally, current commonly used methodologies require relatively large amounts of cell free DNA (cfDNA) input material, thus limiting its application when only small amounts of cfDNA input is available. Experimental Design cfDNA was isolated from whole blood collected from commercially available prostate cancer patients or age-matched healthy donors and evaluated using Predicine’s platform for whole exome sequencing, plasma WES, and compared to the targeted 500 gene PredicineATLAS panel (cfDNA input 10 or 30 ng). Additionally, low-input cfDNA (cfDNA input 10 or 20 ng) was also evaluated for whole genome methylation sequencing using PredicineECM and compared with standard whole genome bisulfite sequencing (WGBS). Results Plasma WES profiling of 30 or 10 ng cfDNA detected variants with mutation allele frequency (MAF) of 1% and above in the entire exome region, which enabled more accurate genome wide copy number variation prediction. All mutations detected using the PredicineATLAS panel that were ≥1% allele frequency were also detected by plasma WES, although low input required greater depth (10 ng, 3,500x) compared with high input (30 ng, 2500x depth). Furthermore, plasma WES identified 1.5 to 15.3x additional mutations compared with the PredicineATLAS panel. PredicineECM methylation analysis was superior to WGBS in reducing DNA damage and GC bias, resulting in increased NGS read mapping rate and quality score. Profiling of 2.5, 5 and 10 ng cfDNA using PredicineECM showed higher mapping rate and quality compared with WGBS profiling of 10 ng cfDNA. Additionally, clustering analysis of CpG methylation using PredicineECM separated tumor samples from normal samples and may serve as additional markers for minimal residue disease (MRD) tracing or early cancer detection. Conclusion In conclusion, we have successfully developed a multi-omics analysis platform for low-input cfDNA that integrates whole exome mutation and whole genome methylation profiling to obtain a comprehensive picture of cancer genomics to enable precision medicine in prostate cancer. This technology can also be applied to other cancers. Citation Format: Raju Kandimalla, Binggang Xiang, Chao Dai, Amy Wang, Pan Du, Shujun Luo, Debbie Liao. Whole exome and whole genome methylation sequencing of low-input cfDNA to implement precision medicine in metastatic castration resistant prostate cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr CC07-01.

Phosphoproteomics Identifies Significant Biomarkers Associated with the Proliferation and Metastasis of Prostate Cancer.

The spider peptide toxins HNTX-III and JZTX-I are a specific inhibitor and activator of TTX-S VGSCs, respectively. They play important roles in regulating MAT-LyLu cell metastasis in prostate cancer. In order to identify key biomarkers involved in the regulation of MAT-LyLu cell metastasis, iTRAQ-based quantitative phosphoproteomics analysis was performed on cells treated with HNTX-III, JZTX-I and blank. A total of 554 unique phosphorylated proteins and 1779 distinct phosphorylated proteins were identified, while 55 and 36 phosphorylated proteins were identified as differentially expressed proteins in HNTX-III and JZTX-I treated groups compared with control groups. Multiple bioinformatics analysis based on quantitative phosphoproteomics data suggested that the differentially expressed phosphorylated proteins and peptides were significantly associated with the migration and invasion of prostate tumors. Specifically, the toxins HNTX-III and JZTX-I have opposite effects on tumor formation and metastasis by regulating the expression and phosphorylation level of causal proteins. Herein, we highlighted three key proteins EEF2, U2AF2 and FLNC which were down-regulated in HNTX-III treated cells and up-regulated in JZTX-I treated cells. They played significant roles in cancer related physiological and pathological processes. The differentially expressed phosphorylated proteins identified in this study may serve as potential biomarkers for precision medicine for prostate cancer in the near future.

SY37-2 Precision medicine in prostate cancer

SY37-2 Precision medicine in prostate cancer

Resistance to second-generation androgen receptor antagonists in prostate cancer.

The introduction of second-generation androgen receptor antagonists (SG-ARAs) has greatly impacted the treatment of metastatic prostate cancer, providing tolerable and efficacious alternatives to chemotherapy. SG-ARAs provide similar therapeutic benefit to abiraterone, a potent CYP17 inhibitor, and do not require the co-administration of prednisone. Despite considerable improvements in clinical outcomes in the settings of both castration sensitivity and castration resistance, the durability of clinical response to the SG-ARAs enzalutamide, apalutamide and darolutamide, similar to abiraterone, is limited by inevitable acquired resistance. Genomic aberrations that confer resistance to SG-ARAs or provide potential alternative treatment modalities have been identified in numerous studies, including alterations of the androgen receptor, DNA repair, cell cycle, PI3K-AKT-mTOR and Wnt-β-catenin pathways. To combat resistance, researchers have explored approaches to optimizing the utility of available treatments, as well as the use of alternative agents with a variety of targets, including AR-V7, AKT, EZH2 and HIF1α. Ongoing research to establish predictive biomarkers for the treatment of tumours with resistance to SG-ARAs led to the approval of the PARP inhibitors olaparib and rucaparib in pre-treated metastatic castration-resistant prostate cancer. The results of ongoing studies will help to shape precision medicine in prostate cancer and further optimize treatment paradigms to maximize clinical outcomes.

TPX2 mediates prostate cancer epithelial-mesenchymal transition through CDK1 regulated phosphorylation of ERK/GSK3β/SNAIL pathway

Prostate cancer with high Gleason grade is prone to metastasis, which is one of the factors that seriously threaten the survival of patients, and it is also a treatment difficulty. In this study, we first revealed the potential connection between TPX2 and prostate cancer metastasis. We found that TPX2 is highly expressed in high-grade prostate cancer and is significantly related to poor prognosis. Depletion of TPX2 can significantly inhibit cell activity and migration, and in vivo experiments show that knockdown of TPX2 can significantly inhibit tumor growth. In terms of mechanism, we found that knocking down TPX2 can inhibit the expression of CDK1, repress the phosphorylation of ERK/GSK3β/SNAIL signaling pathway, and thereby inhibit tumor epithelial-mesenchymal transition. Subsequently, we found that after rescuing TPX2, all related proteins and phenotype changes were restored, and this effect can be inhibited by CDK1 inhibitor, RO-3306. Our findings suggest the potential of TPX2 as an important target in anti-tumor metastasis therapy, which is conducive to precision medicine for prostate cancer.

Clinical implications of genomic evaluations for prostate cancer risk stratification, screening, and treatment: a narrative review.

New classification systems based on molecular features have been introduced to improve precision medicine for prostate cancer (PCa). This review covers the increasing risk of PCa and the differences in response to targeted therapy that are related to specific gene variations. We believe that genomic evaluations will be useful for guiding PCa risk stratification, screening, and treatment. We searched the PubMed and MEDLINE databases for articles related to genomic testing for PCa that were published in 2020 or earlier. There is increasing evidence that germline mutations in DNA repair genes, such as BRCA1/2 or ATM, are closely related to the development and aggressiveness of PCa. Targeted prostate-specific antigen screening based on the presence of germline alterations in DNA repair genes is recommend to achieve an early diagnosis of PCa. In cases of localized PCa, even if it has a favorable risk classification, patients under active surveillance with these gene alterations are likely to develop aggressive PCa. Thus, active treatment may be preferable to active surveillance for these patients. In cases of metastatic castration–resistant PCa, BRCA1/2 and DNA mismatch repair genes may be useful biomarkers for predicting the response to androgen receptor–targeting agents, poly (ADP-ribose) polymerase inhibitors, platinum chemotherapy, prostate-specific membrane antigen–targeted therapy, immunotherapy, and radium-223. Genomic evaluations may allow for risk stratification of patients with PCa based on their molecular features, which may help guide precision medicine for treating PCa.

Abstract 5378: A comparative analysis on the expression of PSA protein in serum and PSA mRNA in circulating tumor cells in prostate cancer

Abstract Introduction Unlike other cancers, prostate cancer has a distinguished biomarker for diagnosis and prognosis which is known as prostate specific antigen (PSA) protein in serum. In the early stage of prostate cancer, PSA protein in serum is highly expressed from primary tumor sites and thereby, the expression of PSA protein can be used in prognosis of prostate cancer during whole progression. However, due to low specificity of serum PSA protein, it raised concerns in over-diagnosis. Due to the advantages of noninvasive, real-time and pain-free for patients, circulating tumor cells (CTCs) is being researched as complementary alternative biomarkers for clinical and molecular analysis of cancer. Some studies reported that the levels of PSA protein and PSA mRNA in prostate cancer tissue are proportional to each other. Other studies showed that the expression level of PSA mRNA in peripheral blood and biochemical recurrence of PSA protein in serum are significant relationship. However, the relevance between PSA protein in serum and PSA mRNA in CTCs has not been clearly researched. In this study, we first report the relevance of the expression levels of PSA protein in serum and PSA mRNA in CTCs. Experimental method and analysis Prostate cancer patients were recruited from healthy donor (HD, n=5), local with non-metastatic stage (n=25), metastatic hormone sensitive prostate cancer (mHSPC, n=9) and metastatic castration-resistance prostate cancer (mCRPC, n=28). CTCs were isolated by high efficiency and purity using microfluidic technology based on lateral magnetophoresis, developed in our laboratory. Total mRNA was extracted from isolated CTC and the expression level of PSA mRNA in CTCs was measured by droplet digital PCR (ddPCR). Then, the expression levels of PSA protein (ng/ml) in serum and PSA mRNA (copies/µl) in CTCs were compared by statistical analysis. Results and discussion The expression of PSA mRNA in CTCs was observed in 40% of localized cancer, 55.56% of mHSPC, 89.29% of mCRPC patients and 0% of HD group. It indicates that the detection rate of PSA mRNA increases with stage of prostate cancer. The expression level of PSA mRNA in CTCs also increased from localized to metastatic stages. Interestingly, it increased very rapidly in mHSPC and mCRPC stages. In 7 of the blood samples of localized stage, the expression levels of PSA mRNA in CTCs were detected and they were not related to serum PSA protein. In mHSPC and mCRPC stage, the expression levels of PSA mRNA in CTCs were respectively detected in 5 and 25 samples, implicating that their expression levels are significantly related to the level of PSA protein in serum. Conclusions This result shows that the expression level of PSA mRNA in CTCs could be used as a new marker along with serum PSA protein in metastatic stages of prostate cancer, and that high-quality CTCs can be used as complementary alternative biomarkers for precision medicine in prostate cancer. Citation Format: Hyungseok Cho, Ki-Ho Han, Jae-Seung Chung. A comparative analysis on the expression of PSA protein in serum and PSA mRNA in circulating tumor cells in prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5378.

KLF5 inhibits STAT3 activity and tumor metastasis in prostate cancer by suppressing IGF1 transcription cooperatively with HDAC1

KLF5 is frequently deleted and downregulated in prostate cancer, and recently it has been reported that KLF5 loss is enriched in the aggressive branches of prostate cancer evolution. However, why KLF5 loss is associated with prostate cancer aggressiveness is still not clear. Herein, we analyzed KLF5 expression in TCGA and GEO database, as well as prostate cancer tissue microarray, and found that KLF5 expression significantly decreased in prostate cancer accompanying with tumor progression; moreover, KLF5 downregulation was associated with shorter survival of patients. Interestingly, we also found that KLF5 expression was obviously lower in prostate cancer metastases than in localized tissues, indicating that KLF5 downregulation is associated with prostate cancer invasion and metastasis. To assess this effect of KLF5, we knocked down KLF5 in prostate cancer cells and found that KLF5 knockdown promoted invasive ability of prostate cancer cells in vitro and in vivo. Moreover, we found that KLF5 downregulation enhanced the expression of IGF1 and STAT3 phosphorylation, while block of IGF1 with antibody decreased the enhancement of STAT3 activity and prostate cancer cell invasive ability by KLF5 knockdown, indicating that KLF5 inhibits prostate cancer invasion through suppressing IGF1/STAT3 pathway. Mechanistically, we found that KLF5 interacted with deacetylase HDAC1 and KLF5 is necessary for the binding of HDAC1 on IGF1 promoter to suppress IGF1 transcription. Taken together, our results indicate that KLF5 could be an important suppressor of prostate cancer invasion and metastasis, because KLF5 could suppress the transcription of IGF1, a tumor cell autocrine cytokine, and its downstream cell signaling to inhibit cell invasive ability, and reveal a novel mechanism for STAT3 activation in prostate cancer. These findings may provide evidence for the precision medicine in prostate cancer.

Challenges, applications and future directions of precision medicine in prostate cancer - the role of organoids and patient-derived xenografts.

To provide a clinically relevant outline of various current precision medicine principles and available evidence on the application and potential for a precision medicine approach in prostate cancer. Narrative review of the current literature in the field. Precision medicine is the concept of individualising patient management based on specific tumour characteristics and biology, rather than traditional histological subtypes. The overall aim is to personalise management to individual patients, to provide the right cancer treatment, to the right patient, at the right time. While the approach aims to improve clinical outcomes, decrease morbidity and improve survival in men with advanced prostate cancer, its clinical application is in its infancy. It does however show great promise in this and other cancers, and will continue to be an area of active research and clinical investigation.

A New Era of Prostate Cancer Precision Medicine.

Prostate cancer is the second most common male cancer affecting Western society. Despite substantial advances in the exploration of prostate cancer biomarkers and treatment strategies, men are over diagnosed with inert prostate cancer, while there is also a substantial mortality from the invasive disease. Precision medicine is the management of treatment profiles across different cancers predicting therapies for individual cancer patients. With strategies including individual genomic profiling and targeting specific cancer pathways, precision medicine for prostate cancer has the potential to impose changes in clinical practices. Some of the recent advances in prostate cancer precision medicine comprise targeting gene fusions, genome editing tools, non-coding RNA biomarkers, and the promise of liquid tumor profiling. In this review, we will discuss these recent scientific advances to scale up these approaches and endeavors to overcome clinical barriers for prostate cancer precision medicine.