Prostate cancer treatment and the relationship of androgen deprivation therapy to cognitive function

Reiss, Allison B.; Saeedullah, Usman; Grossfeld, David; Glass, AG; Pinkhasov, Aaron; Katz, Anne

doi:10.1007/s12094-021-02727-1

Cited by 15 publications

(17 citation statements)

References 97 publications

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“…Prostate cancer is the most prevalent neoplasm among men [ 18 ] due to its high incidence rates and overall good prognosis. The cognitive performance of patients with this cancer has been studied in the context of the association of androgen deprivation therapy (ADT) with cognitive decline [ 19 ] and dementia [ 20 ], which could be explained by testosterone castration levels induced by ADT and the loss of the neuroprotective effect of this hormone [ 21 ]. Patients frequently present advanced age at diagnosis (median age of 67 years [ 22 ]), which is a known risk factor for cognitive impairment [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Cognitive Impairment before Prostate Cancer Treatment

Araújo

Costa

Lopes

et al. 2022

Cancers

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Cognitive impairment is common among patients with different types of cancer, even before cancer treatment, but no data were reported among patients with prostate cancer (PCa), who may be at high risk due to advanced age. This study aims to estimate the prevalence of cognitive impairment before PCa treatment. Between February 2018 and April 2021, the NEON-PC cohort recruited 605 patients with PCa proposed for treatment at the Portuguese Institute of Oncology of Porto. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance. Participants with a MoCA < 1.5 standard deviations (SD) of age- and education-specific normative values were considered to have probable cognitive impairment (PCI) and were referred for a comprehensive neuropsychological assessment. Data from the population-based cohort EPIPorto (n = 351 men aged ≥40 years, evaluated in 2013–2015) were used for comparison. The prevalence of PCI was 17.4% in EPIPorto and 14.7% in NEON-PC (age- and education-adjusted odds ratio: 0.82, 95%CI: 0.58,1.18). Neuropsychological assessment was performed in 63 patients with PCa: 54.0% had cognitive impairment. These results suggest that the impact of PCa on cognitive performance could be negligible in the short term, contrary to what other studies have reported regarding other types of cancer.

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Section: Introductionmentioning

confidence: 99%

Prevalence of Cognitive Impairment before Prostate Cancer Treatment

Araújo

Costa

Lopes

et al. 2022

Cancers

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“…[4][5][6] A growing body of evidence supports a link between ADT and neurocognitive impairment. 7,8 In humans, behavioral and neurologic effects are recognized with an age-related decrease in circulating testosterone levels and cognitive function. 9 A causal relationship between lower testosterone levels and impaired cognitive function has been associated with diminished neuron growth and axonal regeneration.…”

Section: Introductionmentioning

confidence: 99%

“…A growing body of evidence supports a link between ADT and neurocognitive impairment 7,8 . In humans, behavioral and neurologic effects are recognized with an age‐related decrease in circulating testosterone levels and cognitive function 9 .…”

Section: Introductionmentioning

confidence: 99%

Increased cytokine gene expression and cognition risk associated with androgen deprivation therapy

et al. 2022

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Background Androgen deprivation therapy (ADT) is a standard treatment modality for locally advanced, high‐risk, and metastatic hormone‐sensitive prostate cancer. Long‐term ADT treatment likely develops side‐effects that include changes in cognition or onset of dementia. However, the molecular understanding of this effect remains elusive. We attempt to establish a link between ADT and changes in cognitive function using patient databases and bioinformatics analyses. Methods Gene expression profiling was performed using RNA sequencing data from Alzheimer patient cohort and compared with the data from advanced‐stage prostate cancer patients receiving neoadjuvant antiandrogen therapy. Differentially expressed genes (DEGs) were analyzed using the Ingenuity knowledge database. Results A total of 1952 DEGs in the Alzheimer patient cohort and 101 DEGs were identified in ADT treated prostate cancer patients. Comparing both data sets provided a subset of 33 commonly expressed genes involving cytokine‐cytokine signaling with an over representation of cytokine‐cytokine receptor interaction, inflammatory cytokines, signaling by interleukins together with alterations in the circulating lymphocyte repertoire, adaptive immune responses, regulation of cytokine production, and changes in T‐cell subsets. Additionally, lipopolysaccharide, tumor necrosis factor, and toll‐like receptors were identified as upstream transcriptional regulators of these pathways. The most commonly expressed genes viz. IL‐17A, CCL2, IL‐10, IL‐6, IL‐1RN, LIF/LIFR were further validated by quantitative RT‐PCR exhibited higher expression in antiandrogen treated neuronal, glial, and androgen‐responsive prostate cancer cells, compared to no‐androgen antagonist treatment. Conclusions Our findings suggest that changes in cytokine signaling under the influence of ADT in prostate cancer patients may be linked with cognitive impairment presenting new avenues for diagnostic and therapeutic development in combating brain deficits.

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“…Prostate cancer (PrC) has the highest incidence among malignancies in aged Chinese male patients ( 1 ). The growth of PrCs is regulated by androgen ( 2 ). On the other hand, PrC cells may proliferate independently on androgen ( 3 ) and metastasize to distant organs.…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, PrC cells may proliferate independently on androgen ( 3 ) and metastasize to distant organs. Such cases are castration-resistant prostate cancers (CRPCs) ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

Spindle pole body component 25 and platelet-derived growth factor mediate crosstalk between tumor-associated macrophages and prostate cancer cells

Cui

Xu²,

Hu³

et al. 2022

Front. Immunol.

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Tumor-associated macrophages (TAMs) are involved in the growth of prostate cancer (PrC), while the molecular mechanisms underlying the interactive crosstalk between TAM and PrC cells remain largely unknown. Platelet-derived growth factor (PDGF) is known to promote mesenchymal stromal cell chemotaxis to the tumor microenvironment. Recently, activation of spindle pole body component 25 (SPC25) has been shown to promote PrC cell proliferation and is associated with PrC stemness. Here, the relationship between SPC25 and PDGF in the crosstalk between TAM and PrC was investigated. Significant increases in both PDGF and SPC25 levels were detected in PrC specimens compared to paired adjacent normal prostate tissues. A significant correlation was detected between PDGF and SPC25 levels in PrC specimens and cell lines. SPC25 increased PDGF production and tumor cell growth in cultured PrC cells and in xenotransplantation. Mechanistically, SPC25 appeared to activate PDGF in PrC likely through Early Growth Response 1 (Egr1), while the secreted PDGF signaled to TAM through PDGFR on macrophages and polarized macrophages, which, in turn, induced the growth of PrC cells likely through their production and secretion of transforming growth factor β1 (TGFβ1). Thus, our data suggest that SPC25 triggers the crosstalk between TAM and PrC cells via SPC25/PDGF/PDGFR/TGFβ1 receptor signaling to enhance PrC growth.

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Prostate cancer treatment and the relationship of androgen deprivation therapy to cognitive function

Cited by 15 publications

References 97 publications

Prevalence of Cognitive Impairment before Prostate Cancer Treatment

Prevalence of Cognitive Impairment before Prostate Cancer Treatment

Increased cytokine gene expression and cognition risk associated with androgen deprivation therapy

Spindle pole body component 25 and platelet-derived growth factor mediate crosstalk between tumor-associated macrophages and prostate cancer cells

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