Treatment of advanced prostate cancer

Held-Warmkessel, Jeanne

doi:10.1053/sonu.2001.23078

Cited by 9 publications

(10 citation statements)

References 61 publications

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“…The differential expression tool for Slide-seqV2 is available at https://github.com/kharchenkolab/slideseqde. 1 accession number will available after publication of the manuscript.…”

Section: Author Contributionsmentioning

confidence: 99%

“…Some patients present with indolent low-risk prostate tumors that can safely be observed, while others have aggressive high-risk disease that carries a substantial relapse risk even following state-of-the-art treatment. Despite efforts aimed at early detection and improving our current curative-intent therapies, many patients unfortunately experience recurrence and disease progression (1). There remains a significant need to further our understanding of prostate cancer, where biological insights of the prostate tumor microenvironment (TME) may help to identify novel therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Integrated single-cell and spatial transcriptomic analyses unravel the heterogeneity of the prostate tumor microenvironment

Hirz

Mei

Sarkar

et al. 2022

Preprint

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The treatment of primary prostate cancer delicately balances an active surveillance approach for low-risk disease with multimodal treatment including surgery, radiation therapy, and hormonal therapy for high-risk disease. Recurrence and development of metastatic disease remains a clinical problem, without a clear understanding of what drives immune escape and tumor progression. Here, we sought to comprehensively describe the tumor microenvironment of localized prostate cancer contrasting this with adjacent normal samples and healthy controls. We performed single-cell RNA sequencing and high-resolution spatial transcriptomic analysis. This revealed tumor context dependent changes in gene expression. Our data point towards an immune suppressive tumor microenvironment associated with suppressive myeloid populations and exhausted T-cells, in addition to high stromal angiogenic activity. We inferred cell-to-cell relationships at an unprecedented scale for ligand-receptor interactions within undissociated tissue sections. Our work provides a highly detailed and comprehensive resource of the prostate tumor microenvironment as well as tumor-stromal cell interactions.

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“…The differential expression tool for Slide-seqV2 is available at https://github.com/kharchenkolab/slideseqde. 1 accession number will available after publication of the manuscript.…”

Section: Author Contributionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Integrated single-cell and spatial transcriptomic analyses unravel the heterogeneity of the prostate tumor microenvironment

Hirz

Mei

Sarkar

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Some patients present with low-risk prostate tumors that can safely be observed, while others have a high-risk disease that carries a substantial relapse risk even following state-of-the-art treatment. Despite efforts aimed at early detection and improving our current curative-intent therapies, many patients, unfortunately, experience recurrence 1 . There remains a significant need to further our understanding of PCa, where biological insights of the prostate tumor microenvironment (TME) may help to identify novel therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses

et al. 2023

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The treatment of low-risk primary prostate cancer entails active surveillance only, while high-risk disease requires multimodal treatment including surgery, radiation therapy, and hormonal therapy. Recurrence and development of metastatic disease remains a clinical problem, without a clear understanding of what drives immune escape and tumor progression. Here, we comprehensively describe the tumor microenvironment of localized prostate cancer in comparison with adjacent normal samples and healthy controls. Single-cell RNA sequencing and high-resolution spatial transcriptomic analyses reveal tumor context dependent changes in gene expression. Our data indicate that an immune suppressive tumor microenvironment associates with suppressive myeloid populations and exhausted T-cells, in addition to high stromal angiogenic activity. We infer cell-to-cell relationships from high throughput ligand-receptor interaction measurements within undissociated tissue sections. Our work thus provides a highly detailed and comprehensive resource of the prostate tumor microenvironment as well as tumor-stromal cell interactions.

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“…However, overall disease management depends on stage/severity and type of cancer. Surgery, nanotechnology for controlled drug delivery, monoclonal antibody therapy, hormonal therapy, radiotherapy, and chemotherapy are some of the treatment methods (9,10). Chemotherapy (especially when hormonal treatment fails), surgery and radiotherapy are the most commonly used modalities of therapy.…”

Section: Introductionmentioning

confidence: 99%

A molecular docking study of human STEAP2 for the discovery of new potential anti-prostate cancer chemotherapeutic candidates

Ongaba

Christian

Nakiddu

2021

Preprint

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Prostate cancer refers to uncontrolled abnormal cell growth (Cancer) within the prostate gland. The disease is a rising health concern and accounts for 3.8% of all cancer deaths globally. Uganda has one of the highest incidence rates of the disease in Africa being 5.2% and many of the diagnosed patients are found to have advanced stage prostate cancer. This study aimed to use STEAP2 protein (prostate cancer specific biomarker) for the discovery of new lead compounds against prostate cancer. To determine the most likely compound that can bind to STEAP2 protein, we docked the modelled STEAP2 3 Dimension structure against 2466 FDA (Food and Drug Administration) approved drug candidates using Autodock vina. Protein Basic Local Alignment Search Tool (BLASTp) search, Multiple Sequence Alignment (MSA), and phylogenetics were further carried out to analyse the diversity of this marker and determine its conserved domains as suitable target regions. Six promising drug candidates (ligands) were identified of which Triptorelin had the highest binding energy (-12.1 kcal/mol). Leuprolide was the second most promising candidate with a docking energy of -11.2 kcal/mol. All the top 3 of 6 drugs interacted with highly conserved residues Ser-372 and Gly-369 in close proximity with the iron binding domain that was shown to be important for catalysis of metal reduction. The two drugs had earlier been approved for treatment of advanced prostate cancer but with an elusive mode of action. Thanks to this study we now have an insight on how their interaction with STEAP2 might be important during treatment.

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Treatment of advanced prostate cancer

Cited by 9 publications

References 61 publications

Integrated single-cell and spatial transcriptomic analyses unravel the heterogeneity of the prostate tumor microenvironment

Integrated single-cell and spatial transcriptomic analyses unravel the heterogeneity of the prostate tumor microenvironment

Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses

A molecular docking study of human STEAP2 for the discovery of new potential anti-prostate cancer chemotherapeutic candidates

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