Scholars@Duke
Joel Robert Eisner

Joel Robert Eisner

Instructor, Medical Center in the Department of Pharmacology and Cancer Biology
Pharmacology & Cancer Biology

Selected Publications

A phase 1/2a dose-finding study and biomarker assessment of oral lisavanbulin in patients with high-grade glioma or glioblastoma.

Journal Article Cell Rep Med · June 17, 2025 Lisavanbulin is a prodrug of the microtubule-targeting agent avanbulin. Both avanbulin and lisavanbulin have demonstrated significant antitumor activity in several preclinical tumor models including glioblastoma. Previous human studies demonstrated that 48 ... Full text Link to item Cite

Characterization of FGFR Alterations and Activation in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer.

Journal Article Clin Cancer Res · December 2, 2024 PURPOSE: The Genomic Analysis of High-Risk Non-Muscle-Invasive Bladder Cancer (GARNER) study investigated FGFR alteration (ALT) frequency and the clinical outcome relationship with Bacillus Calmette-Guérin (BCG) treatment in high-risk non-muscle-invasive b ... Full text Link to item Cite

The Immunogenomic Landscape of Peripheral High-Dose IL-2 Pharmacodynamics in Patients with Metastatic Renal Cell Carcinoma: A Benchmark for Next-Generation IL-2-Based Immunotherapies.

Journal Article J Immunol · July 1, 2024 High-dose (HD) IL-2 was the first immuno-oncology agent approved for treating advanced renal cell carcinoma and metastatic melanoma, but its use was limited because of substantial toxicities. Multiple next-generation IL-2 agents are being developed to impr ... Full text Link to item Cite

Development of a novel RNA-based fibroblast growth factor receptor response signature (FGFR-PRS) for use in patients with urothelial cancer (UC).

Conference Journal of Clinical Oncology · February 1, 2024 548Background: Interest in FGFR-targeted (FGFRi) therapies for UC or pan-tumor use is growing (ongoing clinical studies include erdafitinib (NCT05316155; NCT04172675; NCT03390504; NCT04083976), LOXO-435 (NCT05614739), and pemigatinib (NCT03914794) followin ... Full text Cite

Phase 1/2a study of PRL-02, a long-acting IM depot injection of abiraterone decanoate, in patients with prostate cancer including those previously treated with enzalutamide.

Journal Article Journal of Clinical Oncology · February 1, 2024 140Background: PRL-02 is a novel long-acting intramuscular (IM) depot injection prodrug of abiraterone (AA) that was designed to provide better safety through lower and less variable plasma exposures. Clinical results show that PRL-02 has a potentially sup ... Full text Cite

Development of a novel RNA-based immune checkpoint inhibitor response signature (ICI-PRS) that avoids standard-of-care (SOC) prognostic signal for use in patients with urothelial cancer (UC).

Conference Journal of Clinical Oncology · January 1, 2024 Background: Immune checkpoint inhibition (ICI) shows great promise, including approval of pembrolizumab, nivolumab and avelumab in urothelial cancer (UC). However, the overall percentage of UC patients with clinical benefit is relatively small, despite bio ... Full text Cite

Association of Antifolate Response Signature Status and Clinical Activity of Pemetrexed-Platinum Chemotherapy in Non-Small Cell Lung Cancer: The Piedmont Study.

Journal Article Clin Cancer Res · August 15, 2023 PURPOSE: The Piedmont study is a prospectively designed retrospective evaluation of a new 48-gene antifolate response signature (AF-PRS) in patients with locally advanced/metastatic nonsquamous (NS) non-small cell lung cancer (NSCLC) treated with pemetrexe ... Full text Link to item Cite

Lisavanbulin in patients with recurrent glioblastoma: Phase 2a results and a consolidated analysis of response-predictive biomarkers.

Conference Journal of Clinical Oncology · June 1, 2023 2044 Background: Lisavanbulin (BAL101553, prodrug of BAL27862) destabilizes microtubules and promotes tumor cell death by modulating the spindle assembly checkpoint. BAL27862 is a lipophilic small molecule shown in rodents to pen ... Full text Cite

Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer.

Journal Article Br J Cancer · September 2022 PURPOSE: Radiation therapy (RT) and hormone receptor (HR) inhibition are used for the treatment of HR-positive breast cancers; however, little is known about the interaction of the androgen receptor (AR) and estrogen receptor (ER) in response to RT in AR-p ... Full text Link to item Cite

Distinct Predictive Immunogenomic Profiles of Response to Immune Checkpoint Inhibitors and IL2: A Real-world Evidence Study of Patients with Advanced Renal Cancer.

Journal Article Cancer Res Commun · August 2022 UNLABELLED: Recombinant human high-dose IL2 (HD-IL2; aldesleukin) was one of the first approved immune-oncology agents based upon clinical activity in renal cell carcinoma (RCC) and metastatic melanoma but use was limited due to severe toxicity. Next-gener ... Full text Link to item Cite

Abiraterone decanoate (PRL-02): Pharmacology of a single intramuscular (IM) depot injection compared to oral abiraterone acetate (AA) in intact male rats.

Conference Journal of Clinical Oncology · February 20, 2022 160 Background: Oral AA is a standard of care for metastatic prostate cancer. The recommended daily AA 1000 mg dose produces high peak and low trough plasma concentrations that are associated with safety issues (e.g., hepatotoxic ... Full text Cite

Fibroblast growth factor receptor 3 alterations and response to immune checkpoint inhibition in metastatic urothelial cancer: a real world experience.

Journal Article Br J Cancer · October 2021 BACKGROUND: FGFR3-altered urothelial cancer (UC) correlates with a non-T cell-inflamed phenotype and has therefore been postulated to be less responsive to immune checkpoint blockade (ICB). Preclinical work suggests FGFR3 signalling may suppress pathways s ... Full text Link to item Cite

Activity of Combined Androgen Receptor Antagonism and Cell Cycle Inhibition in Androgen Receptor Positive Triple Negative Breast Cancer.

Journal Article Mol Cancer Ther · June 2021 Triple-negative breast cancer (TNBC) is an aggressive subtype, with a peak recurrence rate within the first few years after diagnosis. Few targeted therapies are available to treat this breast cancer subtype, defined by the lack of estrogen receptor (ER) a ... Full text Link to item Cite

Expression of the Androgen Receptor Governs Radiation Resistance in a Subset of Glioblastomas Vulnerable to Antiandrogen Therapy.

Journal Article Mol Cancer Ther · October 2020 New approaches are needed to overcome intrinsic therapy resistance in glioblastoma (GBM). Because GBMs exhibit sexual dimorphism and are reported to express steroid hormone receptors, we reasoned that signaling through the androgen receptor (AR) could medi ... Full text Link to item Cite

Abstract 6267: Repurposing antiandrogens to overcome therapy resistance in androgen receptor-positive glioblastoma

Conference Cancer Research · August 15, 2020 AbstractNew approaches are needed to overcome intrinsic therapy resistance in glioblastoma (GBM). Because GBMs exhibit sexual dimorphism and are reported to express steroid hormone receptors, we reasoned tha ... Full text Cite

Phase 2 Study of Seviteronel (INO-464) in Patients With Metastatic Castration-Resistant Prostate Cancer After Enzalutamide Treatment.

Journal Article Clin Genitourin Cancer · August 2020 BACKGROUND: Seviteronel was being developed by Innocrin Pharmaceuticals as a selective cytochrome P450c17a (CYP17) 17,20-lyase (lyase) inhibitor and androgen receptor antagonist with activity against prostate cancer cells in vitro and in vivo. This open-la ... Full text Link to item Cite

Seviteronel, a Novel CYP17 Lyase Inhibitor and Androgen Receptor Antagonist, Radiosensitizes AR-Positive Triple Negative Breast Cancer Cells.

Journal Article Front Endocrinol (Lausanne) · 2020 Increased rates of locoregional recurrence (LR) have been observed in triple negative breast cancer (TNBC) despite multimodality therapy, including radiation (RT). Recent data suggest inhibiting the androgen receptor (AR) may be an effective radiosensitizi ... Full text Link to item Cite

A population pharmacokinetic analysis of the oral CYP17 lyase and androgen receptor inhibitor seviteronel in patients with advanced/metastatic castration-resistant prostate cancer or breast cancer.

Journal Article Cancer Chemother Pharmacol · October 2019 PURPOSE: Seviteronel is an orally-administered selective cytochrome P450c17a 17,20-lyase and androgen receptor inhibitor with anti-tumor activity in vitro and in vivo, and clinical activity in men with advanced castration-resistant prostate cancer (CRPC) a ... Full text Link to item Cite

Abstract P5-05-05: Targeting the androgen receptor with seviteronel, a CYP17 lyase and AR inhibitor, in triple negative breast cancer

Conference Cancer Research · February 15, 2019 AbstractBackground: Androgen receptor (AR) protein is expressed across breast cancer (BC) subtypes, including up to 50% of triple negative breast cancers (TNBC) and it is often maintained in metastases. Our ... Full text Cite

Male breast cancer: a disease distinct from female breast cancer.

Journal Article Breast Cancer Res Treat · January 2019 PURPOSE: Male breast cancer (BC) is rare, representing approximately 1% of cancers that occur in men and approximately 1% of all BCs worldwide. Because male BC is rare, not much is known about the disease, and treatment recommendations are typically extrap ... Full text Link to item Cite

Phase I Study of Seviteronel, a Selective CYP17 Lyase and Androgen Receptor Inhibitor, in Men with Castration-Resistant Prostate Cancer.

Journal Article Clin Cancer Res · November 1, 2018 Purpose: Seviteronel (INO-464) is a selective cytochrome P450c17a (CYP17) 17,20-lyase (lyase) and androgen receptor (AR) inhibitor with antitumor activity in vitro and in vivo This open-label phase I clinical study evaluated the safety, tolerability, pharm ... Full text Link to item Cite

Phase 1 study of seviteronel, a selective CYP17 lyase and androgen receptor inhibitor, in women with estrogen receptor-positive or triple-negative breast cancer.

Journal Article Breast Cancer Res Treat · August 2018 PURPOSE: Seviteronel (INO-464) is an oral, selective cytochrome P450c17a (CYP17) 17,20-lyase (lyase) and androgen receptor inhibitor with in vitro and in vivo anti-tumor activity. This open-label phase 1 clinical study evaluated safety, tolerability, pharm ... Full text Link to item Cite

Harnessing a Different Dependency: How to Identify and Target Androgen Receptor-Positive Versus Quadruple-Negative Breast Cancer.

Journal Article Horm Cancer · April 2018 The androgen receptor (AR) is a promising therapeutic target for a subset of triple-negative breast cancers (TNBCs) in which AR is expressed. However, the mechanistic action of AR and the degree to which primary and metastatic tumors depend on AR, both bef ... Full text Link to item Cite

Androgen receptor antagonism drives cytochrome P450 17A1 inhibitor efficacy in prostate cancer.

Journal Article J Clin Invest · June 1, 2017 The clinical utility of inhibiting cytochrome P450 17A1 (CYP17), a cytochrome p450 enzyme that is required for the production of androgens, has been exemplified by the approval of abiraterone for the treatment of castration-resistant prostate cancer (CRPC) ... Full text Link to item Cite

Abstract P3-14-04: Effects of the dual selective CYP17 lyase inhibitor and androgen receptor (AR) antagonist, VT-464, on AR+ and ER+ tumor models in vitro and in vivo

Conference Cancer Research · February 15, 2016 AbstractVT-464 is a lyase-selective inhibitor of the dual-activity CYP17A1 enzyme that is required for the synthesis of androgens and estrogens in the gonads, adrenals, and tumors. In addition to its role as ... Full text Cite

Abstract OT2-01-03: A phase 1/2 study of once-daily oral VT-464 in patients with advanced androgen receptor (AR) positive triple negative (TNBC) or estrogen receptor (ER) positive breast cancer (BC)

Conference Cancer Research · February 15, 2016 AbstractVT-464, an oral dual lyase-selective CYP17 inhibitor and AR antagonist (wild-type and mutated forms [e.g., F876L and T877A]), is in multiple Phase (Ph) 2 studies as treatment for men with castration- ... Full text Cite

Objective response of the dual CYP17-Lyase (L) inhibitor / androgen receptor (AR) antagonist, VT-464, in patients with CRPC.

Conference Journal of Clinical Oncology · January 10, 2016 273 Background: VT-464 is an oral, CYP17-L inhibitor and non-clinically an antagonist of the AR and its variants associated with clinical resistance to enzalutamide (ENZ) and abiraterone (AA). The safety, tolerability and initial ... Full text Cite

Once-nightly (QD) dual CYP17-Lyase (L) inhibitor / androgen receptor (AR) antagonist VT-464 in patients with CRPC.

Conference Journal of Clinical Oncology · January 10, 2016 343 Background: VT-464 is an oral, CYP17-L inhibitor and non-clinically an antagonist of the AR and its variants associated with clinical resistance to enzalutamide (ENZ) and abiraterone (AA). The safety, tolerability and initial ... Full text Cite

Cardiovascular safety profile of VT-464 in patients (pts) with castrate-resistant prostate cancer (CRPC).

Conference Journal of Clinical Oncology · January 10, 2016 198 Background: VT-464 is a dual selective inhibitor of CYP17,20 lyase and an androgen receptor antagonist in development for the treatment of CRPC. In early clinical testing, several pts receiving VT-464 in 28-day cycles were no ... Full text Cite

Direct effects of the selective CYP17 lyase (L) inhibitor, VT-464, on the androgen receptor (AR) and its oral activity in an F876L tumor mouse xenograft model.

Conference Journal of Clinical Oncology · March 1, 2015 263 Background: MDV3100 inhibits binding of androgens to AR and abiraterone is known to block androgen production through CYP17 inhibition; both are effective treatments for castration-resistant prostate cancer (CRPC, yet cross-r ... Full text Cite

The oral CYP17-Lyase (L) inhibitor VT-464 in patients with CRPC.

Conference Journal of Clinical Oncology · March 1, 2015 187 Background: VT-464 is an oral, non-steroidal inhibitor of CYP17-L and an antagonist of androgen receptor (AR) variants F876L and T877A which are associated with resistance to enzalutamide (ENZ) and abiraterone/prednisone (AA) ... Full text Cite

Highly-selective 4-(1,2,3-triazole)-based P450c17a 17,20-lyase inhibitors.

Journal Article Bioorg Med Chem Lett · June 1, 2014 The orally-active CYP17A1 inhibitor abiraterone acetate (AA) decreases adrenal and intratumoral androgen biosynthesis and is an effective agent for the treatment of prostate cancer. Abiraterone potently inhibits both reactions catalyzed by CYP17, the 17α-h ... Full text Link to item Cite

The enzymology of the selective CYP17 lyase inhibitor, VT-464, and its effects in castration-resistant prostate cancer (CRPC) models.

Conference Journal of Clinical Oncology · February 1, 2014 158 Background: CRPC typically responds to anti-androgen therapy but resistance is common. CYP17 inhibitors that block lyase (L) and not hydroxylase (H), do not require prednisone, and may delay tumor resistance are needed. VT-46 ... Full text Cite

Abstract 4772: Efficacy of VT-464, a novel selective inhibitor of cytochrome P450 17,20-lyase, in castrate-resistant prostate cancer models.

Conference Cancer Research · April 15, 2013 AbstractCytochrome P450 17α-hydroxylase /17,20-lyase (CYP17) is a validated treatment target for metastatic castrate-resistant prostate cancer (mCRPC). Abiraterone acetate (AA; Zytiga) inhibits 17α-hydroxyla ... Full text Cite

Insulin Resistance and Impaired Insulin Secretion in Prenatally Androgenized Male Rhesus Monkeys

Conference The Journal of Clinical Endocrinology & Metabolism · December 2004 Full text Cite