Understanding and targeting prostate cancer cell heterogeneity and plasticity

Tang, Dean G.

doi:10.1016/j.semcancer.2021.11.001

Cited by 42 publications

(43 citation statements)

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“…Prostate cancer (PCa) is the most common malignant tumor in the male reproductive system, usually diagnosed in the elderly (age > 65 years) [ 16 , 17 ] and ranking the second leading cause of cancer-related death in men [ 18 ]. The normal human prostate is a walnut-sized, pseudostratified two-layer epithelial glandular organ that contains an inner layer of secretory luminal epithelial cells surrounded by a layer of basal cells interspersed with rare neuroendocrine cells [ 19 , 20 ] ( Figure 1 ). The luminal or glandular cells, characterized by the expression of cytokeratin 8 (CK8), androgen receptor (AR), prostate-specific antigen (PSA), constitute the ‘functional’ exocrine compartment of the prostate, secreting into the glandular lumen prostatic fluid as a major component of the ejaculate [ 19 ].…”

Section: Prostate Tumor As An Organ Of Increasingly Deregulated Diffe...mentioning

confidence: 99%

“…The normal human prostate is a walnut-sized, pseudostratified two-layer epithelial glandular organ that contains an inner layer of secretory luminal epithelial cells surrounded by a layer of basal cells interspersed with rare neuroendocrine cells [ 19 , 20 ] ( Figure 1 ). The luminal or glandular cells, characterized by the expression of cytokeratin 8 (CK8), androgen receptor (AR), prostate-specific antigen (PSA), constitute the ‘functional’ exocrine compartment of the prostate, secreting into the glandular lumen prostatic fluid as a major component of the ejaculate [ 19 ]. The basal cells are CK5 + , CK14 + , and p63 + and AR − cells ( Figure 2 ).…”

Section: Prostate Tumor As An Organ Of Increasingly Deregulated Diffe...mentioning

confidence: 99%

“…Tumorigenesis resembles abnormal organogenesis, and prostate tumor is an organ of increasingly deregulated differentiation. The aggressiveness or the level of malignancy of primary PCa in a biopsy can be pathologically assessed by a combined GS grading system with respect to their degree of differentiation, i.e., the higher the GS, the more malignant (less differentiated) the tumor is [ 19 , 22 ]. This most commonly used grading system in the clinic relies on the architectural pattern of cancerous glands, with Gleason pattern 1—representing most well-differentiated glandular structures and Gleason pattern 5—representing the most poorly differentiated cells (lack of glandular structures).…”

Section: Prostate Tumor As An Organ Of Increasingly Deregulated Diffe...mentioning

confidence: 99%

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Prostate cancer as a dedifferentiated organ: androgen receptor, cancer stem cells, and cancer stemness

Liu

Puzanov

et al. 2022

Essays in Biochemistry

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Cancer progression is characterized and driven by gradual loss of a differentiated phenotype and gain of stem cell-like features. In prostate cancer (PCa), androgen receptor (AR) signaling is important for cancer growth, progression, and emergence of therapy resistance. Targeting the AR signaling axis has been, over the decades, the mainstay of PCa therapy. However, AR signaling at the transcription level is reduced in high-grade cancer relative to low-grade PCa and loss of AR expression promotes a stem cell-like phenotype, suggesting that emergence of resistance to AR-targeted therapy may be associated with loss of AR signaling and gain of stemness. In the present mini-review, we first discuss PCa from the perspective of an abnormal organ with increasingly deregulated differentiation, and discuss the role of AR signaling during PCa progression. We then focus on the relationship between prostate cancer stem cells (PCSCs) and AR signaling. We further elaborate on the current methods of using transcriptome-based stemness-enriched signature to evaluate the degree of oncogenic dedifferentiation (cancer stemness) in pan-cancer datasets, and present the clinical significance of scoring transcriptome-based stemness across the spectrum of PCa development. Our discussions highlight the importance to evaluate the dynamic changes in both stem cell-like features (stemness score) and AR signaling activity across the PCa spectrum.

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Section: Prostate Tumor As An Organ Of Increasingly Deregulated Diffe...mentioning

confidence: 99%

Section: Prostate Tumor As An Organ Of Increasingly Deregulated Diffe...mentioning

confidence: 99%

Section: Prostate Tumor As An Organ Of Increasingly Deregulated Diffe...mentioning

confidence: 99%

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Prostate cancer as a dedifferentiated organ: androgen receptor, cancer stem cells, and cancer stemness

Liu

Puzanov

et al. 2022

Essays in Biochemistry

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“…High-grade tumors (GS9-10) with lymph node (LN) metastasis are treated with drugs named AR signaling inhibitors (ARSIs). In general, ARSIs comprise two subclasses [ 2 ]. The first class aims to block AR productions in the testis (e.g., orchiectomy or using LHRH agonists or antagonists) or adrenal gland (e.g., abiraterone acetate), and the former is often called androgen deprivation therapy (ADT).…”

Section: Introduction: Pca Cell Heterogeneity Pcscs and Crpcmentioning

confidence: 99%

“…Therapy resistance is significantly influenced by intra-tumor heterogeneity [ 4 ]. Over the course of PCa development and progression, from treatment-naïve primary tumors to CRPC to metastatic CRPC (mCRPC), significant heterogeneity in AR and PSA expression have been demonstrated [ 2 , 5 , 6 ].…”

Section: Introduction: Pca Cell Heterogeneity Pcscs and Crpcmentioning

confidence: 99%

MicroRNA-34a, Prostate Cancer Stem Cells, and Therapeutic Development

Liu

Dougherty

et al. 2022

Cancers

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Prostate cancer (PCa) is a highly heterogeneous disease and typically presents with multiple distinct cancer foci. Heterogeneity in androgen receptor (AR) expression levels in PCa has been observed for decades, from untreated tumors to castration-resistant prostate cancer (CRPC) to disseminated metastases. Current standard-of-care therapies for metastatic CRPC can only extend life by a few months. Cancer stem cells (CSCs) are defined as a subpopulation of cancer cells that exists in almost all treatment-naive tumors. Additionally, non-CSCs may undergo cellular plasticity to be reprogrammed to prostate cancer stem cells (PCSCs) during spontaneous tumor progression or upon therapeutic treatments. Consequently, PCSCs may become the predominant population in treatment-resistant tumors, and the “root cause” for drug resistance. microRNA-34a (miR-34a) is a bona fide tumor-suppressive miRNA, and its expression is dysregulated in PCa. Importantly, miR-34a functions as a potent CSC suppressor by targeting many molecules essential for CSC survival and functions, which makes it a promising anti-PCSC therapeutic. Here, we conducted a comprehensive literature survey of miR-34a in the context of PCa and especially PCSCs. We provided an updated overview on the mechanisms of miR-34a regulation followed by discussing its tumor suppressive functions in PCa. Finally, based on current advances in miR-34a preclinical studies in PCa, we offered potential delivery strategies for miR-34a-based therapeutics for treating advanced PCa.

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Composition‐Reinforced Polydopamine Nanoenzyme for Improved Impairment of Prostatitis‐Damaged Sexual Behavior and Enhanced Anti‐Prostate Cancer

Wang,

Mao,

Song

et al. 2024

Adv Funct Materials

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Inflammation is pivotal in the pathogenesis and progression of the most challenging diseases and even cancer. Nanomedicine‐based strategy can be referred as a distinct solution to this complicated clinical obstacle by proposing an elaborated combination of effective therapeutic performances on inflammation and cancer. Herein, 2,2,6,6‐tetramethylpiperidine‐1‐oxyl doped polydopamine nanoparticles, termed as TPDA NPs, with the significantly improved reactive oxygen/nitrogen species (RO/NSs) scavenging performance and enhanced photothermal efficiency are designed and synthesized by constructing donor‐acceptor pairs, for prostate diseases treatment including anti‐inflammation and anti‐tumor. Benefiting from mimicking multi‐natural enzymes, including superoxide dismutase, catalase, peroxidase, and glutathione peroxidase, TPDA NPs can inhibit the NF‐κB signaling pathways by downregulating the CD36 expression for the treatment of oxidative stress‐induced prostatitis. Especially, TPDA NPs can improve the prostatitis‐associated impairment of sexual behavior. By virtue of the enhanced photothermal‐conversion efficiency, TPDA NPs ablate prostate cancer and simultaneously decrease inflammatory reaction. Therefore, this work provides a “three birds with one shot” paradigm to utilize rationally designed TPDA NPs for efficient management of prostate diseases.

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Understanding and targeting prostate cancer cell heterogeneity and plasticity

Cited by 42 publications

References 340 publications

Prostate cancer as a dedifferentiated organ: androgen receptor, cancer stem cells, and cancer stemness

Prostate cancer as a dedifferentiated organ: androgen receptor, cancer stem cells, and cancer stemness

MicroRNA-34a, Prostate Cancer Stem Cells, and Therapeutic Development

Composition‐Reinforced Polydopamine Nanoenzyme for Improved Impairment of Prostatitis‐Damaged Sexual Behavior and Enhanced Anti‐Prostate Cancer

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