Biomedicines

Research

17 pages, 2287 KiB

Open AccessArticle

Rapid Androgen-Responsive Proteome Is Involved in Prostate Cancer Progression

by Jong-Kwang Kim, Jae-Hun Jung, Dong-Hoon Shin, Hye-Jin You, Seho Cha, Bo-Seul Song, Jae-Young Joung, Weon-Seo Park, Kwang-Pyo Kim and Jae-Kyung Myung

Biomedicines 2021, 9(12), 1877; https://doi.org/10.3390/biomedicines9121877 - 10 Dec 2021

Cited by 3 | Viewed by 2556

Abstract

Androgen exerts its functions by binding with an androgen receptor (AR). It can activate many signaling pathways that are important to the progression of castration-resistant prostate cancer (CRPC). Here, we characterized the rapid proteomic changes seen at 5, 15, 30, and 60 min [...] Read more.

Androgen exerts its functions by binding with an androgen receptor (AR). It can activate many signaling pathways that are important to the progression of castration-resistant prostate cancer (CRPC). Here, we characterized the rapid proteomic changes seen at 5, 15, 30, and 60 min after the androgen treatment of VCaP cells via the tandem mass tag (TMT) labeling strategy. A total of 5529 proteins were successfully identified and quantified. Dynamic time profiling of protein expression patterns allowed us to identify five protein clusters involved in various stages of androgen-initiated signal transmission and processing. More details of protein functions and localization patterns, and our elucidation of an AR-interacting protein network, were obtained. Finally, we validated the expression level of AR-regulated proteins known to be significantly regulated in CRPC patients using the mouse xenograft model and patient samples. Our work offers a systematic analysis of the rapid proteomic changes induced by androgen and provides a global view of the molecular mechanisms underlying CRPC progression. Full article

(This article belongs to the Special Issue Novel Strategy for Treating Castration-Resistant Prostate Cancer)

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15 pages, 3811 KiB

Open AccessArticle

Hydralazine and Enzalutamide: Synergistic Partners against Prostate Cancer

by Nair Lopes, Mariana Brütt Pacheco, Diana Soares-Fernandes, Margareta P. Correia, Vânia Camilo, Rui Henrique and Carmen Jerónimo

Biomedicines 2021, 9(8), 976; https://doi.org/10.3390/biomedicines9080976 - 7 Aug 2021

Cited by 11 | Viewed by 3451

Abstract

Advanced prostate cancers frequently develop resistance to androgen-deprivation therapy with serious implications for patient survival. Considering their importance in this type of neoplasia, epigenetic modifications have drawn attention as alternative treatment strategies. The aim of this study was to assess the antitumoral effects [...] Read more.

Advanced prostate cancers frequently develop resistance to androgen-deprivation therapy with serious implications for patient survival. Considering their importance in this type of neoplasia, epigenetic modifications have drawn attention as alternative treatment strategies. The aim of this study was to assess the antitumoral effects of the combination of hydralazine, a DNA methylation inhibitor, with enzalutamide, an antagonist of the androgen receptor, in prostate cancer cell lines. Several biological parameters, such as cell viability, proliferation, DNA damage, and apoptosis, as well as clonogenic and invasive potential, were evaluated. The individual treatments with hydralazine and enzalutamide exerted growth-inhibitory effects in prostate cancer cells and their combined treatment displayed synergistic effects. The combination of these two drugs was very effective in decreasing malignant features of prostate cancer and may become an alternative therapeutic option for prostate cancer patient management. Full article

(This article belongs to the Special Issue Novel Strategy for Treating Castration-Resistant Prostate Cancer)

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15 pages, 3553 KiB

Open AccessArticle

HOXB5 Overexpression Is Associated with Neuroendocrine Differentiation and Poor Prognosis in Prostate Cancer

by Yohei Sekino, Quoc Thang Pham, Kohei Kobatake, Hiroyuki Kitano, Kenichiro Ikeda, Keisuke Goto, Shogo Inoue, Tetsutaro Hayashi, Masaki Shiota, Wataru Yasui and Jun Teishima

Biomedicines 2021, 9(8), 893; https://doi.org/10.3390/biomedicines9080893 - 26 Jul 2021

Cited by 5 | Viewed by 2846

Abstract

Homeobox genes function as master regulatory transcription factors during embryogenesis. HOXB5 is known to play an important role in several cancers. However, the biological role of HOXB5 in prostate cancer (PCa) is not fully elucidated. This study aimed to analyze the expression and [...] Read more.

Homeobox genes function as master regulatory transcription factors during embryogenesis. HOXB5 is known to play an important role in several cancers. However, the biological role of HOXB5 in prostate cancer (PCa) is not fully elucidated. This study aimed to analyze the expression and function of HOXB5 and involvement of HOXB5 in neuroendocrine differentiation in PCa. Immunohistochemistry showed that 56 (43.8%) of 128 cases of localized PCa were positive for HOXB5. HOXB5-positive cases were associated with poor prostate-specific antigen recurrence-free survival after prostatectomy. Among 74 cases of metastatic PCa, 43 (58.1%) were positive for HOXB5. HOXB5 expression was higher in metastatic PCa than that in localized PCa. HOXB5 knockdown suppressed cell growth and invasion, but HOXB5 overexpression increased cell growth and invasion in PCa cell lines. Furthermore, HOXB5 regulated RET expression. Gene set enrichment analysis revealed that Nelson androgen response gene set was enriched in low HOXB5 expression group. RB1 knockout increased HOXB5 expression. Of note, additional p53 knockdown further increased HOXB5 expression in RB1 knockout cells. In silico analysis showed that HOXB5 expression was increased in neuroendocrine PCa (NEPC). These results suggest that HOXB5 may be a promising prognostic marker after prostatectomy and is involved in progression to NEPC. Full article

(This article belongs to the Special Issue Novel Strategy for Treating Castration-Resistant Prostate Cancer)

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11 pages, 1952 KiB

Open AccessArticle

NRG1 Genetic Variant Influences the Efficacy of Androgen-Deprivation Therapy in Men with Prostate Cancer

by Shu-Pin Huang, Yei-Tsung Chen, Lih-Chyang Chen, Cheng-Hsueh Lee, Chao-Yuan Huang, Chia-Cheng Yu, Victor C. Lin, Te-Ling Lu and Bo-Ying Bao

Biomedicines 2021, 9(5), 528; https://doi.org/10.3390/biomedicines9050528 - 10 May 2021

Cited by 3 | Viewed by 2460

Abstract

Neuregulins (NRGs) activate receptor tyrosine kinases of the ErbB family, and play essential roles in the proliferation, survival, and differentiation of normal and malignant tissue cells. We hypothesized that genetic variants of NRG signalling pathway genes may influence treatment outcomes in prostate cancer. [...] Read more.

Neuregulins (NRGs) activate receptor tyrosine kinases of the ErbB family, and play essential roles in the proliferation, survival, and differentiation of normal and malignant tissue cells. We hypothesized that genetic variants of NRG signalling pathway genes may influence treatment outcomes in prostate cancer. To test this hypothesis, we performed a comprehensive analysis to evaluate the associations of 459 single-nucleotide polymorphisms in 19 NRG pathway genes with cancer-specific survival (CSS), overall survival (OS), and progression-free survival (PFS) in 630 patients with prostate cancer receiving androgen-deprivation therapy (ADT). After multivariate Cox regression and multiple testing correction, we found that NRG1 rs144160282 C > T is significantly associated with worsening CSS, OS, and PFS during ADT. Further analysis showed that low expression of NRG1 is closely related to prostate cancer, as indicated by a high Gleason score, an advanced stage, and a shorter PFS rate. Meta-analysis of 16 gene expression datasets of 1,081 prostate cancer samples and 294 adjacent normal samples indicate lower NRG1 expression in the former compared with the latter (p < 0.001). These results suggest that NRG1 rs144160282 might be a prognostic predictor of the efficacy of ADT. Further studies are required to confirm the significance of NRG1 as a biomarker and therapeutic target for prostate cancer. Full article

(This article belongs to the Special Issue Novel Strategy for Treating Castration-Resistant Prostate Cancer)

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16 pages, 2012 KiB

Open AccessArticle

Mucosa-Associated Lymphoid Tissue 1 Is an Oncogene Inducing Cell Proliferation, Invasion, and Tumor Growth via the Upregulation of NF-κB Activity in Human Prostate Carcinoma Cells

by Ke-Hung Tsui, Kang-Shuo Chang, Hsin-Ching Sung, Shu-Yuan Hsu, Yu-Hsiang Lin, Chen-Pang Hou, Pei-Shan Yang, Chien-Lun Chen, Tsui-Hsia Feng and Horng-Heng Juang

Biomedicines 2021, 9(3), 250; https://doi.org/10.3390/biomedicines9030250 - 3 Mar 2021

Cited by 15 | Viewed by 2929

Abstract

Prostate cancer is one of the most common seen malignancies and the leading cause of cancer-related death among men. Given the importance of early diagnosis and treatment, it is worth to identify a potential novel therapeutic target for prostate cancer. Mucosa-associated lymphoid tissue [...] Read more.

Prostate cancer is one of the most common seen malignancies and the leading cause of cancer-related death among men. Given the importance of early diagnosis and treatment, it is worth to identify a potential novel therapeutic target for prostate cancer. Mucosa-associated lymphoid tissue 1 (MALT1) is a novel gene involved in nuclear factor κB (NF-κB) signal transduction by acting as an adaptor protein and paracaspase, with an essential role in inflammation and tumorigenesis in many cancers. This study investigated the functions and the potential regulatory mechanisms of MALT1 in the human prostate cancer cells. We found that MALT1 is abundant in prostate cancer tissues. MALT1 facilitated NF-κB subunits (p50 and p65) nuclear translocation to induce gene expression of interleukin 6 (IL-6) and C-X-C motif chemokine 5 (CXCL5) in prostate carcinoma cells. MALT1 promoted cell proliferation, invasion, and tumor growth in vitro and in vivo. MALT1 enhanced NF-κB activity in prostate carcinoma cells; moreover, NF-κB induced MALT1 expression determined by reporter and immunoblot assays, implying there is a positive feedback loop between MALT1 and NF-κB. In conclusion, MALT1 is a NF-κB-induced oncogene in the human prostate carcinoma cells. Full article

(This article belongs to the Special Issue Novel Strategy for Treating Castration-Resistant Prostate Cancer)

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15 pages, 9249 KiB

Open AccessArticle

Bacterial Genotoxin-Coated Nanoparticles for Radiotherapy Sensitization in Prostate Cancer

by Yu-An Chen, Yi-Ru Lai, Hui-Yu Wu, Yen-Ju Lo, Yu-Fang Chang, Chiu-Lien Hung, Chun-Jung Lin, U-Ging Lo, Ho Lin, Jer-Tsong Hsieh, Cheng-Hsun Chiu, Yu-Hsin Lin and Chih-Ho Lai

Biomedicines 2021, 9(2), 151; https://doi.org/10.3390/biomedicines9020151 - 4 Feb 2021

Cited by 10 | Viewed by 2866

Abstract

Prostate cancer (PCa) is one of the most commonly diagnosed cancers in men and usually becomes refractory because of recurrence and metastasis. CD44, a transmembrane glycoprotein, serves as a receptor for hyaluronic acid (HA). It has been found to be abundantly expressed in [...] Read more.

Prostate cancer (PCa) is one of the most commonly diagnosed cancers in men and usually becomes refractory because of recurrence and metastasis. CD44, a transmembrane glycoprotein, serves as a receptor for hyaluronic acid (HA). It has been found to be abundantly expressed in cancer stem cells (CSCs) that often exhibit a radioresistant phenotype. Cytolethal distending toxin (CDT), produced by Campylobacter jejuni, is a tripartite genotoxin composed of CdtA, CdtB, and CdtC subunits. Among the three, CdtB acts as a type I deoxyribonuclease (DNase I), which creates DNA double-strand breaks (DSBs). Nanoparticles loaded with antitumor drugs and specific ligands that recognize cancerous cell receptors are promising methods to overcome the therapeutic challenges. In this study, HA-decorated nanoparticle-encapsulated CdtB (HA-CdtB-NPs) were prepared and their targeted therapeutic activity in radioresistant PCa cells was evaluated. Our results showed that HA-CdtB-NPs sensitized radioresistant PCa cells by enhancing DSB and causing G2/M cell-cycle arrest, without affecting the normal prostate epithelial cells. HA-CdtB-NPs possess maximum target specificity and delivery efficiency of CdtB into the nucleus and enhance the effect of radiation in radioresistant PCa cells. These findings demonstrate that HA-CdtB-NPs exert target specificity accompanied with radiomimetic activity and can be developed as an effective strategy against radioresistant PCa. Full article

(This article belongs to the Special Issue Novel Strategy for Treating Castration-Resistant Prostate Cancer)

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13 pages, 3089 KiB

Open AccessArticle

Roles of Interleukin-1 Receptor Antagonist in Prostate Cancer Progression

by Yu-Ching Fan, Kuan-Der Lee and Yuan-Chin Tsai

Biomedicines 2020, 8(12), 602; https://doi.org/10.3390/biomedicines8120602 - 13 Dec 2020

Cited by 13 | Viewed by 3480

Abstract

Background: Inflammation is known to promote tumor formation and progression; however, we found a natural anti-inflammatory factor, interleukin (IL)-1 receptor antagonist (IL1RN), in a mouse transgenic adenocarcinoma of the mouse prostate (TRAMP)-C1-derived tumor microenvironment (TME). We sought to characterize the functions of the [...] Read more.

Background: Inflammation is known to promote tumor formation and progression; however, we found a natural anti-inflammatory factor, interleukin (IL)-1 receptor antagonist (IL1RN), in a mouse transgenic adenocarcinoma of the mouse prostate (TRAMP)-C1-derived tumor microenvironment (TME). We sought to characterize the functions of the IL1RN-secreting cells in the TME. Methods: We compared tumors collected from two syngeneic mouse models and isolated tumor-infiltrating leukocytes (TILs) with different cluster of differentiation 11b (CD11b) statuses. We examined the proliferation functions of the TILs and the IL1RN using several approaches, including a colony-formation assay and DNA synthesis levels. Results: We demonstrated that CD11b-deficient TILs (TILs/CD11b⁻) secreted the IL1RN and promoted proliferation by analyzing conditioned media. In addition to mouse TRAMP-C1, proliferation functions of the IL1RN were confirmed in several human castration-resistant prostate cancer (CRPC) cell lines and one normal epithelial cell line. The androgen-sensitive lymph node carcinoma of the prostate (LNCaP) cell line showed cytotoxic responses to IL1β treatment and androgen-dependent regulation of IL-1 receptor type 1 (IL1R1), while the C4-2 CRPC cell line did not. IL1RN rescued LNCaP cells from the cytotoxic effects of IL1β/IL1R1 signaling. Conclusions: Our results support TILs/CD11b⁻ cells being able to protect androgen-dependent cells from inflammatory damage and promote the malignant progression of prostate cancers partly through the IL1RN in the TME. Full article

(This article belongs to the Special Issue Novel Strategy for Treating Castration-Resistant Prostate Cancer)

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Review

Jump to: Research, Other

11 pages, 622 KiB

Open AccessReview

Definition of Castrate Resistant Prostate Cancer: New Insights

by Juan Morote, Adriana Aguilar, Jacques Planas and Enrique Trilla

Biomedicines 2022, 10(3), 689; https://doi.org/10.3390/biomedicines10030689 - 17 Mar 2022

Cited by 33 | Viewed by 10789

Abstract

The term castrate resistant prostate cancer (CRPC) was initially proposed by the Prostate Cancer Working Group 2 in 2008 to define the state of clinical and/or biochemical progression of prostate cancer (PCa) in an environment with very low serum testosterone concentration. Clinical progression [...] Read more.

The term castrate resistant prostate cancer (CRPC) was initially proposed by the Prostate Cancer Working Group 2 in 2008 to define the state of clinical and/or biochemical progression of prostate cancer (PCa) in an environment with very low serum testosterone concentration. Clinical progression is based on the radiological imaging proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) adapted to PCa. Biochemical progression is defined as an over 25% increase in serum prostate-specific antigen within two consecutive measurements separated by at least one week, and an absolute value above 2.0 ng/mL. Finally, the castrate environment is usually defined as a serum testosterone concentration maintained below 50 ng/dL or 1.7 nmol/dL. This definition does not incorporate the new and more accurate imaging modalities to assess clinical progression and the capability of the new biochemical measurements to assess the true castration environment. Ga-68-PSMA-11 PET CT/MRI and whole-body MRI are the new imaging modalities that should replace the classic thoracic CT scan, abdomino-pelvic CT scan, and technetium 99-m bone scintigraphy. In addition, Ga-68-PSMA-11 PET is the current basis for the new therapies targeting metastatic sites. Moreover, the current methods for measuring the very low serum testosterone concentrations in clinical laboratories are the widespread chemiluminescent assays, which are inappropriate, while LC-MSMS is the only method recommended to assess the castrate environment. In addition, recent research shows that serum luteinising hormone concentration associates better than serum testosterone with the castration environment, even when it is measured with LC-MSMS. In summary, the current definition of CRPC seems outdated. An extensive update to diagnose true CRPC is also needed to differentiate CRPC men with M0 (non-metastatic) from those with M1 (metastatic) CRPC. WC: 277. Full article

(This article belongs to the Special Issue Novel Strategy for Treating Castration-Resistant Prostate Cancer)

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13 pages, 905 KiB

Open AccessReview

Novel Treatment Strategy Using Second-Generation Androgen Receptor Inhibitors for Non-Metastatic Castration-Resistant Prostate Cancer

by Doo Yong Chung, Jee Soo Ha and Kang Su Cho

Biomedicines 2021, 9(6), 661; https://doi.org/10.3390/biomedicines9060661 - 9 Jun 2021

Cited by 9 | Viewed by 3240

Abstract

Non-metastatic castration-resistant prostate cancer (nmCRPC) is defined by a progressively rising prostate-specific antigen level, despite a castrate level of testosterone, in the absence of obvious radiologic evidence of metastatic disease on conventional imaging modalities. As a significant proportion of patients with nmCRPC develop [...] Read more.

Non-metastatic castration-resistant prostate cancer (nmCRPC) is defined by a progressively rising prostate-specific antigen level, despite a castrate level of testosterone, in the absence of obvious radiologic evidence of metastatic disease on conventional imaging modalities. As a significant proportion of patients with nmCRPC develop metastatic diseases, the therapeutic goals of physicians for these patients are to delay metastasis development, preserve quality of life, and increase overall survival (OS). Since 2018, the treatment of nmCRPC has changed dramatically with the introduction of second-generation androgen receptor inhibitors, such as enzalutamide (ENZA), apalutamide (APA), and darolutamide (DARO). These drugs demonstrated substantial improvements in metastasis-free survival (MFS) and OS in phase III randomized clinical trials. In addition, these drugs have an excellent safety profile, preserve quality of life, and can delay disease-related symptoms. A recently published indirect meta-analysis reported that APA and ENZA showed better findings in MFS and that DARO had relatively fewer adverse effects. However, in the absence of a direct comparison, careful interpretation is required. Thus, APA, ENZA, and DARO should be considered the new standard drugs for treating nmCRPC. Full article

(This article belongs to the Special Issue Novel Strategy for Treating Castration-Resistant Prostate Cancer)

15 pages, 1055 KiB

Open AccessReview

¹⁷⁷Lu-PSMA Therapy in Metastatic Castration-Resistant Prostate Cancer

by Yasemin Sanli, Duygu Has Simsek, Oner Sanli, Rathan M. Subramaniam and Ayse Tuba Kendi

Biomedicines 2021, 9(4), 430; https://doi.org/10.3390/biomedicines9040430 - 15 Apr 2021

Cited by 16 | Viewed by 5527

Abstract

The aim of this narrative review is to evaluate the current status of ¹⁷⁷Lu-PSMA (prostate specific membrane antigen) therapy for metastatic castration-resistant prostate cancer (mCRPC) in the light of the current literature. We also addressed patient preparation, therapy administration and side effect [...] Read more.

The aim of this narrative review is to evaluate the current status of ¹⁷⁷Lu-PSMA (prostate specific membrane antigen) therapy for metastatic castration-resistant prostate cancer (mCRPC) in the light of the current literature. We also addressed patient preparation, therapy administration and side effect profiles. ¹⁷⁷Lu-PSMA therapy efficacy was assessed by using prospective trials, meta-analyses and major retrospective trials. Predictors of efficacy were also mentioned. Although there are some different approaches regarding the use of ¹⁷⁷Lu-PSMA therapy in different countries, this type of therapy is generally safe, with a low toxicity profile. From the oncological point of view, a PSA (prostate specific antigen) decline of ≥50% was seen in 10.6–69% of patients with mCRPC; whereas progression-free survival (PFS) was reported to be 3–13.7 months in different studies. Consequently, ¹⁷⁷Lu-PSMA therapy is a promising treatment in patients with mCRPC, with good clinical efficacy, even in heavily pretreated patients with multiple lines of systemic therapy. Currently, there are ongoing clinical trials in the United States, including a phase III multicenter FDA registration trial. Full article

(This article belongs to the Special Issue Novel Strategy for Treating Castration-Resistant Prostate Cancer)

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19 pages, 1644 KiB

Open AccessReview

Undesirable Status of Prostate Cancer Cells after Intensive Inhibition of AR Signaling: Post-AR Era of CRPC Treatment

by Tomoyuki Makino, Kouji Izumi and Atsushi Mizokami

Biomedicines 2021, 9(4), 414; https://doi.org/10.3390/biomedicines9040414 - 12 Apr 2021

Cited by 19 | Viewed by 4266

Abstract

Recent advances in prostate cancer (PC) research unveiled real androgen receptor (AR) functions in castration-resistant PC (CRPC). Moreover, AR still accelerates PC cell proliferation via the activation of several mechanisms (e.g., mutation, variants, and amplifications in CRPC). New-generation AR signaling-targeted agents, inhibiting extremely [...] Read more.

Recent advances in prostate cancer (PC) research unveiled real androgen receptor (AR) functions in castration-resistant PC (CRPC). Moreover, AR still accelerates PC cell proliferation via the activation of several mechanisms (e.g., mutation, variants, and amplifications in CRPC). New-generation AR signaling-targeted agents, inhibiting extremely the activity of AR, were developed based on these incontrovertible mechanisms of AR-induced CRPC progression. However, long-term administration of AR signaling-targeted agents subsequently induces the major problem that AR (complete)-independent CRPC cells present neither AR nor prostate-specific antigen, including neuroendocrine differentiation as a subtype of AR-independent CRPC. Moreover, there are few treatments effective for AR-independent CRPC with solid evidence. This study focuses on the transformation mechanisms of AR-independent from AR-dependent CRPC cells and potential treatment strategy for AR-independent CRPC and discusses them based on a review of basic and clinical literature. Full article

(This article belongs to the Special Issue Novel Strategy for Treating Castration-Resistant Prostate Cancer)

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20 pages, 361 KiB

Open AccessReview

Changing the History of Prostate Cancer with New Targeted Therapies

by Susana Hernando Polo, Diana Moreno Muñoz, Adriana Carolina Rosero Rodríguez, Jorge Silva Ruiz, Diana Isabel Rosero Rodríguez and Felipe Couñago

Biomedicines 2021, 9(4), 392; https://doi.org/10.3390/biomedicines9040392 - 6 Apr 2021

Cited by 20 | Viewed by 4584

Abstract

The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) is changing due to the emergence of new targeted therapies for the treatment of different molecular subtypes. Some biomarkers are described as potential molecular targets different from classic androgen receptors (AR). Approximately 20–25% of [...] Read more.

The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) is changing due to the emergence of new targeted therapies for the treatment of different molecular subtypes. Some biomarkers are described as potential molecular targets different from classic androgen receptors (AR). Approximately 20–25% of mCRPCs have somatic or germline alterations in DNA repair genes involved in homologous recombination. These subtypes are usually associated with more aggressive disease. Inhibitors of the enzyme poly ADP ribose polymerase (PARPi) have demonstrated an important benefit in the treatment of these subtypes of tumors. However, tumors that resistant to PARPi and wildtype BRCA tumors do not benefit from these therapies. Recent studies are exploring drug combinations with phosphatidylinositol-3-kinase (PI3K) or protein kinase B (AKT) inhibitors, as mechanisms to overcome resistance or to induce BRCAness and synthetic lethality. This article reviews various different novel strategies to improve outcomes in patients with prostate cancer. Full article

(This article belongs to the Special Issue Novel Strategy for Treating Castration-Resistant Prostate Cancer)

11 pages, 261 KiB

Open AccessReview

Novel Strategies for Treating Castration-Resistant Prostate Cancer

by David Ka-Wai Leung, Peter Ka-Fung Chiu, Chi-Fai Ng and Jeremy Yuen-Chun Teoh

Biomedicines 2021, 9(4), 339; https://doi.org/10.3390/biomedicines9040339 - 27 Mar 2021

Cited by 23 | Viewed by 3094

Abstract

The development of castration resistance is an inevitable pathway for the vast majority of patients with advanced prostate cancer. Recently, there have been significant breakthroughs in the understanding and management options of castration-resistant prostate cancer. Three novel hormonal agents showed survival benefits in [...] Read more.

The development of castration resistance is an inevitable pathway for the vast majority of patients with advanced prostate cancer. Recently, there have been significant breakthroughs in the understanding and management options of castration-resistant prostate cancer. Three novel hormonal agents showed survival benefits in non-metastatic patients. As for metastatic disease, there was an even wider range of management options being investigated. This review summarized advances in the management of castration-resistant prostate cancer (CRPC) including emerging data on novel imaging techniques and treatment strategies. Full article

(This article belongs to the Special Issue Novel Strategy for Treating Castration-Resistant Prostate Cancer)

Other

Jump to: Research, Review

18 pages, 3080 KiB

Open AccessSystematic Review

¹⁷⁷Lu-PSMA Radioligand Therapy Is Favorable as Third-Line Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

by Finn E. von Eyben, Kalevi Kairemo, Channing Paller, Manuela Andrea Hoffmann, Giovanni Paganelli, Irene Virgolini and Giandomenico Roviello

Biomedicines 2021, 9(8), 1042; https://doi.org/10.3390/biomedicines9081042 - 19 Aug 2021

Cited by 11 | Viewed by 4315

Abstract

In this systematic review and network meta-analysis (NMA), we aimed to assess the benefits and harms of third-line (L3) treatments in randomized controlled trials (RCTs) of patients with metastatic castration-resistant prostate cancer (mCRPC). Two reviewers searched for publications from 1 January 2006 to [...] Read more.

In this systematic review and network meta-analysis (NMA), we aimed to assess the benefits and harms of third-line (L3) treatments in randomized controlled trials (RCTs) of patients with metastatic castration-resistant prostate cancer (mCRPC). Two reviewers searched for publications from 1 January 2006 to 30 June 2021. The review analyzed seven RCTs that included 3958 patients and eight treatments. Treatment with prostate-specific membrane antigen (PSMA)-based radioligand therapy (PRLT) resulted in a 1.3-times-higher rate of median PSA decline ≥50% than treatment with abiraterone, enzalutamide, mitoxantrone, or cabazitaxel (p = 0.00001). The likelihood was 97.6% for PRLT to bring about the best PSA response, out of the examined treatments. PRLT resulted in a 1.1-times-higher six-month rate of median radiographic progression-free survival. Treatment with PRLT in the VISION trial resulted in 1.05-times-higher twelve-month median overall survival than L3 treatment with cabazitaxel in other RCTs. PRLT more often resulted in severe thrombocytopenia and less often in severe leukopenia than did cabazitaxel. In conclusion, for patients with mCRPC, L3 treatment with PRLT is highly effective and safe. Full article

(This article belongs to the Special Issue Novel Strategy for Treating Castration-Resistant Prostate Cancer)

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