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  1. Article ; Online: Resolute Progress Down a Long and Winding Road Leads to the Promised Land of Prostate-Specific Membrane Antigen-Based Therapies for Prostate Cancer.

    Denmeade, Samuel R

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2024  Volume 42, Issue 7, Page(s) 852–856

    MeSH term(s) Male ; Humans ; Prostate ; Prostatic Neoplasms/therapy ; Prostate-Specific Antigen
    Chemical Substances Prostate-Specific Antigen (EC 3.4.21.77)
    Language English
    Publishing date 2024-01-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.23.02310
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1847: Show issues Location:
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    Zs.MO 650: Show issues

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  2. Article ; Online: First, do no harm: The unclear benefit of lifelong castration for patients with metastatic prostate cancer.

    Sena, Laura A / Wang, Hao / Denmeade, Samuel R

    The Prostate

    2023  Volume 83, Issue 12, Page(s) 1127–1132

    MeSH term(s) Male ; Humans ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/pathology ; Castration ; Androgen Antagonists/therapeutic use
    Chemical Substances Androgen Antagonists
    Language English
    Publishing date 2023-05-27
    Publishing country United States
    Document type Editorial ; Research Support, Non-U.S. Gov't
    ZDB-ID 604707-5
    ISSN 1097-0045 ; 0270-4137
    ISSN (online) 1097-0045
    ISSN 0270-4137
    DOI 10.1002/pros.24582
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    Zs.A 1608: Show issues Location:
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  3. Article: Bipolar androgen therapy in the treatment of prostate cancer.

    Denmeade, Samuel R

    Clinical advances in hematology & oncology : H&O

    2018  Volume 16, Issue 6, Page(s) 408–411

    MeSH term(s) Androgen Antagonists/administration & dosage ; Androgen Antagonists/adverse effects ; Androgen Antagonists/therapeutic use ; Androgens/administration & dosage ; Androgens/adverse effects ; Androgens/pharmacokinetics ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Clinical Trials as Topic ; Humans ; Male ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/drug therapy ; Treatment Outcome
    Chemical Substances Androgen Antagonists ; Androgens
    Language English
    Publishing date 2018-08-06
    Publishing country United States
    Document type Interview
    ZDB-ID 2271951-9
    ISSN 1543-0790
    ISSN 1543-0790
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6505: Show issues Location:
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  4. Article ; Online: Fatty Acid Synthesis in Prostate Cancer: Vulnerability or Epiphenomenon?

    Sena, Laura A / Denmeade, Samuel R

    Cancer research

    2021  Volume 81, Issue 17, Page(s) 4385–4393

    Abstract: Tumor metabolism supports the energetic and biosynthetic needs of rapidly proliferating cancer cells and modifies intra- and intercellular signaling to enhance cancer cell invasion, metastasis, and immune evasion. Prostate cancer exhibits unique ... ...

    Abstract Tumor metabolism supports the energetic and biosynthetic needs of rapidly proliferating cancer cells and modifies intra- and intercellular signaling to enhance cancer cell invasion, metastasis, and immune evasion. Prostate cancer exhibits unique metabolism with high rates of
    MeSH term(s) Adipogenesis ; Animals ; Biomarkers/metabolism ; Biomarkers, Tumor/metabolism ; Cell Proliferation ; Disease Progression ; Fatty Acids/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Lipogenesis ; Male ; Mice ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Prostatic Neoplasms/metabolism ; Receptors, Androgen/metabolism ; Signal Transduction
    Chemical Substances Biomarkers ; Biomarkers, Tumor ; Fatty Acids ; Receptors, Androgen
    Language English
    Publishing date 2021-06-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 1432-1
    ISSN 1538-7445 ; 0008-5472
    ISSN (online) 1538-7445
    ISSN 0008-5472
    DOI 10.1158/0008-5472.CAN-21-1392
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Uh III Zs.135/5: Show issues Location:
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  5. Article ; Online: Targeting the spectrum of immune checkpoints in prostate cancer.

    Sena, Laura A / Denmeade, Samuel R / Antonarakis, Emmanuel S

    Expert review of clinical pharmacology

    2021  Volume 14, Issue 10, Page(s) 1253–1266

    Abstract: ... ...

    Abstract Introduction
    MeSH term(s) Cancer Vaccines/administration & dosage ; Drug Resistance, Neoplasm ; Humans ; Immune Checkpoint Inhibitors/administration & dosage ; Immunotherapy/methods ; Male ; Molecular Targeted Therapy ; Patient Selection ; Prostate-Specific Antigen/blood ; Prostatic Neoplasms/immunology ; Prostatic Neoplasms/therapy ; Tissue Extracts/administration & dosage
    Chemical Substances Cancer Vaccines ; Immune Checkpoint Inhibitors ; Tissue Extracts ; sipuleucel-T (8Q622VDR18) ; Prostate-Specific Antigen (EC 3.4.21.77)
    Language English
    Publishing date 2021-07-15
    Publishing country England
    Document type Journal Article ; Review
    ISSN 1751-2441
    ISSN (online) 1751-2441
    DOI 10.1080/17512433.2021.1949287
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The testosterone paradox of advanced prostate cancer: mechanistic insights and clinical implications.

    Kumar, Rajendra / Sena, Laura A / Denmeade, Samuel R / Kachhap, Sushant

    Nature reviews. Urology

    2022  Volume 20, Issue 5, Page(s) 265–278

    Abstract: The discovery of the benefits of castration for prostate cancer treatment in 1941 led to androgen deprivation therapy, which remains a mainstay of the treatment of men with advanced prostate cancer. However, as early as this original publication, the ... ...

    Abstract The discovery of the benefits of castration for prostate cancer treatment in 1941 led to androgen deprivation therapy, which remains a mainstay of the treatment of men with advanced prostate cancer. However, as early as this original publication, the inevitable development of castration-resistant prostate cancer was recognized. Resistance first manifests as a sustained rise in the androgen-responsive gene, PSA, consistent with reactivation of the androgen receptor axis. Evaluation of clinical specimens demonstrates that castration-resistant prostate cancer cells remain addicted to androgen signalling and adapt to chronic low-testosterone states. Paradoxically, results of several studies have suggested that treatment with supraphysiological levels of testosterone can retard prostate cancer growth. Insights from these studies have been used to investigate administration of supraphysiological testosterone to patients with prostate cancer for clinical benefits, a strategy that is termed bipolar androgen therapy (BAT). BAT involves rapid cycling from supraphysiological back to near-castration testosterone levels over a 4-week cycle. Understanding how BAT works at the molecular and cellular levels might help to rationalize combining BAT with other agents to achieve increased efficacy and tumour responses.
    MeSH term(s) Male ; Humans ; Prostatic Neoplasms/therapy ; Testosterone/therapeutic use ; Androgens/therapeutic use ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Androgen Antagonists/therapeutic use ; Prostate-Specific Antigen ; Receptors, Androgen
    Chemical Substances Testosterone (3XMK78S47O) ; Androgens ; Androgen Antagonists ; Prostate-Specific Antigen (EC 3.4.21.77) ; Receptors, Androgen
    Language English
    Publishing date 2022-12-21
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 2493737-X
    ISSN 1759-4820 ; 1759-4812
    ISSN (online) 1759-4820
    ISSN 1759-4812
    DOI 10.1038/s41585-022-00686-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6030: Show issues Location:
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  7. Article ; Online: Bipolar Androgen Therapy Followed by Androgen Receptor Inhibition as Sequential Therapy for Prostate Cancer.

    Denmeade, Samuel R / Sena, Laura A / Wang, Hao / Antonarakis, Emmanuel S / Markowski, Mark C

    The oncologist

    2023  Volume 28, Issue 6, Page(s) 465–473

    Abstract: Inhibition of androgen receptor (AR) signaling has been the mainstay of treatment of advanced prostate cancer (PCa) for the past 80 years. Combination and sequential AR-inhibiting therapies are highly effective palliative therapy, but they are not ... ...

    Abstract Inhibition of androgen receptor (AR) signaling has been the mainstay of treatment of advanced prostate cancer (PCa) for the past 80 years. Combination and sequential AR-inhibiting therapies are highly effective palliative therapy, but they are not curative. All patients eventually develop resistance to primary castrating therapy [ie, castration-resistant PCa (CRPC)]. At this point, they are treated with subsequent lines of secondary AR inhibitory therapies. However, resistance to these agents also develops and patients progress to a state we have termed complete androgen inhibition-resistant PCa. This phase of the disease is associated with poor prognosis. At this point, treatment shifts to non-hormonal cytotoxic therapies (eg, chemotherapy and radiopharmaceuticals). However, the majority of PCas remain addicted to signaling through AR throughout the course of the disease. Resistant PCa cells adaptively upregulate AR activity, despite castration and AR inhibitors, via mechanisms such as AR overexpression, gene amplification, mutation, and expression of ligand-independent variants to permit sustained liganded and non-liganded AR signaling. Studies dating back nearly 30 years indicate that high expression of AR induced by prolonged castration becomes a vulnerability of CRPC cells in vitro and in mouse xenografts to supraphysiologic androgen (SPA), which induces cell death and growth arrest in this context. Based on these studies, we developed a counterintuitive treatment called bipolar androgen therapy (BAT) for patients with CRPC, in which SPA is administered intermittently to result in cycling of serum testosterone from the polar extremes of supraphysiologic to near-castrate levels. This rapid cycling is intended to disrupt the adaptive of AR regulation associated with chronic exposure to high or low levels of testosterone, while simultaneously targeting the spectrum of AR expression present in heterogeneous CRPC tumors. We have now tested BAT in >250 patients with CRPC. Here we present a review of these clinical studies, which have demonstrated collectively that BAT can be safely given to men with CRPC, improves quality of life, and produces therapeutic responses in ~30% of patients. As expected, resistance to BAT is associated with adaptive downregulation of AR expression. Intriguingly, this downregulation is associated with restoration of sensitivity to subsequent AR inhibitor therapies.
    MeSH term(s) Male ; Humans ; Animals ; Mice ; Androgens/metabolism ; Androgens/pharmacology ; Androgens/therapeutic use ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/genetics ; Quality of Life ; Testosterone/therapeutic use ; Cell Line, Tumor
    Chemical Substances Androgens ; Receptors, Androgen ; Testosterone (3XMK78S47O)
    Language English
    Publishing date 2023-04-07
    Publishing country England
    Document type Review ; Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1409038-7
    ISSN 1549-490X ; 1083-7159
    ISSN (online) 1549-490X
    ISSN 1083-7159
    DOI 10.1093/oncolo/oyad055
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    Zs.A 4845: Show issues Location:
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    Zs.MO 494: Show issues

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  8. Article: Serial bipolar androgen therapy (sBAT) using cyclic supraphysiologic testosterone (STP) to treat metastatic castration-resistant prostate cancer (mCRPC).

    Isaacs, John T / Brennen, W Nathaniel / Denmeade, Samuel R

    Annals of translational medicine

    2020  Volume 7, Issue Suppl 8, Page(s) S311

    Language English
    Publishing date 2020-01-03
    Publishing country China
    Document type Editorial ; Comment
    ZDB-ID 2893931-1
    ISSN 2305-5847 ; 2305-5839
    ISSN (online) 2305-5847
    ISSN 2305-5839
    DOI 10.21037/atm.2019.10.32
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  9. Article ; Online: Mipsagargin: The Beginning-Not the End-of Thapsigargin Prodrug-Based Cancer Therapeutics.

    Isaacs, John T / Brennen, William Nathaniel / Christensen, Søren Brøgger / Denmeade, Samuel R

    Molecules (Basel, Switzerland)

    2021  Volume 26, Issue 24

    Abstract: Søren Brøgger Christensen isolated and characterized the cell-penetrant sesquiterpene lactone Thapsigargin (TG) from the ... ...

    Abstract Søren Brøgger Christensen isolated and characterized the cell-penetrant sesquiterpene lactone Thapsigargin (TG) from the fruit
    MeSH term(s) Animals ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/therapeutic use ; Clinical Trials, Phase II as Topic ; Humans ; Neoplasm Proteins/metabolism ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Prodrugs/pharmacokinetics ; Prodrugs/therapeutic use ; Thapsigargin/pharmacokinetics ; Thapsigargin/therapeutic use
    Chemical Substances Antineoplastic Agents ; Neoplasm Proteins ; Prodrugs ; Thapsigargin (67526-95-8)
    Language English
    Publishing date 2021-12-09
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules26247469
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    Zs.MO 81: Show issues

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  10. Article ; Online: Updated analyses for RESTORE cohort C: A trial of bipolar androgen therapy for patients with newly castration-resistant prostate cancer.

    Sena, Laura A / Wang, Tingchang / Wang, Hao / Markowski, Mark C / Antonarakis, Emmanuel S / Denmeade, Samuel R

    European journal of cancer (Oxford, England : 1990)

    2022  Volume 181, Page(s) 23–25

    MeSH term(s) Humans ; Male ; Androgen Antagonists/therapeutic use ; Androgens ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Receptors, Androgen
    Chemical Substances Androgen Antagonists ; Androgens ; Prostate-Specific Antigen (EC 3.4.21.77) ; Receptors, Androgen
    Language English
    Publishing date 2022-12-09
    Publishing country England
    Document type Clinical Trial ; Letter ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 82061-1
    ISSN 1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
    ISSN (online) 1879-0852
    ISSN 0277-5379 ; 0959-8049 ; 0964-1947
    DOI 10.1016/j.ejca.2022.12.001
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    Zs.A 456: Show issues Location:
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    Zs.MO 583: Show issues

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