Beyond the androgen receptor II: New approaches to understanding and treating metastatic prostate cancer; Report from the 2017 Coffey‐Holden Prostate Cancer Academy Meeting

Miyahira, Andrea K.; Cheng, Heather H.; Abida, Wassim; Ellis, Leigh; Harshman, Lauren C.; Spratt, Daniel E.; Simons, Jonathan W.; Soule, Howard R.

doi:10.1002/pros.23424

Cited by 11 publications

(8 citation statements)

References 103 publications

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“…2 Histone modification is one of the most important types of epigenetic changes and is extremely crucial for cancer progression, including prostate cancer. [3][4][5][6] Histone acetylation/deacetylation that alters chromatin structure plays a key role in the regulation of transcription, cell-cycle progression, and developmental events. 2,7,8 HDAC6, belonging to class IIb of the HDACs family, is a structurally and functionally unique HDAC family member containing a ubiquitinbinding zinc-finger domain and two active deacetylase domains.…”

Section: Introductionmentioning

confidence: 99%

A novel HDAC6 inhibitor interferes microtubule dynamics and spindle assembly checkpoint and sensitizes cisplatin‐induced apoptosis in castration‐resistant prostate cancer

Ye,

Leu,

Yeh

et al. 2024

The Prostate

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BackgroundMetastatic castration‐resistant prostate cancer (CRPC), the most refractory prostate cancer, inevitably progresses and becomes unresponsive to hormone therapy, revealing a pressing unmet need for this disease. Novel agents targeting HDAC6 and microtubule dynamics can be a potential anti‐CRPC strategy.MethodsCell proliferation was examined in CRPC PC‐3 and DU‐145 cells using sulforhodamine B assay and anchorage‐dependent colony formation assay. Flow cytometric analysis of propidium iodide staining was used to determine cell‐cycle progression. Cell‐based tubulin polymerization assay and confocal immunofluorescence microscopic examination determine microtubule assembly/disassembly status. Protein expressions were determined using Western blot analysis.ResultsA total of 82 novel derivatives targeting HDAC6 were designed and synthesized, and Compound 25202 stood out, showing the highest efficacy in blocking HDAC6 (IC50, 3.5 nM in enzyme assay; IC50, 1.0 μM in antiproliferative assay in CRPC cells), superior to tubastatin A (IC50, 5.4 μM in antiproliferative assay). The selectivity and superiority of 25202 were validated by examining the acetylation of both α‐tubulin and histone H3, detecting cell apoptosis and HDACs enzyme activity assessment. Notably, 25202 but not tubastatin A significantly decreased HDAC6 protein expression. 25202 prolonged mitotic arrest through the detection of cyclin B1 upregulation, Cdk1 activation, mitotic phosphoprotein levels, and Bcl‐2 phosphorylation. Compound 25202 did not mimic docetaxel in inducing tubulin polymerization but disrupted microtubule organization. Compound 25202 also increased the phosphorylation of CDC20, BUB1, and BUBR1, indicating the activation of the spindle assembly checkpoint (SAC). Moreover, 25202 profoundly sensitized cisplatin‐induced cell death through impairment of cisplatin‐evoked DNA damage response and DNA repair in both ATR–Chk1 and ATM–Chk2 pathways.ConclusionThe data suggest that 25202 is a novel selective and potent HDAC6 inhibitor. Compound 25202 blocks HDAC6 activity and interferes microtubule dynamics, leading to SAC activation and mitotic arrest prolongation that eventually cause apoptosis of CRPC cells. Furthermore, 25202 sensitizes cisplatin‐induced cell apoptosis through impeding DNA damage repair pathways.

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Section: Introductionmentioning

confidence: 99%

A novel HDAC6 inhibitor interferes microtubule dynamics and spindle assembly checkpoint and sensitizes cisplatin‐induced apoptosis in castration‐resistant prostate cancer

Ye,

Leu,

Yeh

et al. 2024

The Prostate

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“…The CHPCA Meeting uses a unique discussion‐focused conference format inspired by the former NCI Prouts Neck Meeting on Prostate Cancer, 1 to foster dialogue and debate surrounding the most leading‐edge and critical topics in prostate cancer research and other fields with strong potential to seed new understandings of prostate cancer biology and new treatment paradigms 2–9 . The CHPCA Meeting was named in honor of prostate cancer research pioneers, Dr. Stuart Holden and the late Dr. Donald Coffey.…”

Section: Introductionmentioning

confidence: 99%

Exploring new frontiers in prostate cancer research: Report from the 2022 Coffey−Holden prostate cancer academy meeting

et al. 2022

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Introduction The 2022 Coffey−Holden Prostate Cancer Academy (CHPCA) Meeting, “Exploring New Frontiers in Prostate Cancer Research,” was held from June 23 to 26, 2022, at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA. Methods The CHPCA Meeting is an annual discussion‐oriented scientific conference organized by the Prostate Cancer Foundation, that focuses on emerging and next‐step topics deemed critical for making the next major advances in prostate cancer research and clinical care. The 2022 CHPCA Meeting included 35 talks over 10 sessions and was attended by 73 academic investigators. Results Major topic areas discussed at the meeting included: prostate cancer diversity and disparities, the impact of social determinants on research and patient outcomes, leveraging real‐world and retrospective data, development of artificial intelligence biomarkers, androgen receptor (AR) signaling biology and new strategies for targeting AR, features of homologous recombination deficient prostate cancer, and future directions in immunotherapy and nuclear theranostics. Discussion This article summarizes the scientific presentations from the 2022 CHPCA Meeting, with the goal that dissemination of this knowledge will contribute to furthering global prostate cancer research efforts.

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“…The CHPCA Meeting is a discussion oriented invitation‐only scientific conference that focuses on cutting edge research from prostate cancer and other intersecting fields that may accelerate new treatments for patients with advanced prostate cancer 1–7 . This Meeting, held ~annually, was named for prostate cancer research pioneers, Dr. Stuart Holden and the late Dr. Donald Coffey.…”

Section: Introductionmentioning

confidence: 99%

Prostate cancer research in the 21st century; report from the 2021 Coffey‐Holden prostate cancer academy meeting

et al. 2021

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Introduction The 2021 Coffey‐Holden Prostate Cancer Academy (CHPCA) Meeting, “Prostate Cancer Research in the 21st Century,” was held virtually, from June 24–25, 2021. Methods The CHPCA Meeting is organized by the Prostate Cancer Foundation as a unique discussion‐oriented meeting focusing on critical topics in prostate cancer research envisioned to bridge the next major advances in prostate cancer biology and treatment. The 2021 CHPCA Meeting was virtually attended by 89 investigators and included 31 talks over nine sessions. Results Major topic areas discussed at the meeting included: cancer genomics and sequencing, functional genomic approaches to studying mediators of plasticity, emerging signaling pathways in metastatic castration resistant prostate cancer, Wnt signaling biology and the challenges of targeted therapy, clonal hematopoiesis, neuroendocrine cell plasticity and antitumor immunity, cancer immunotherapy and its synergizers, and imaging the tumor microenvironment and metabolism. Discussion This meeting report summarizes the research presented at the 2021 CHPCA Meeting. We hope that publication of this knowledge will accelerate new understandings and the development of new biomarkers and treatments for prostate cancer.

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Beyond the androgen receptor II: New approaches to understanding and treating metastatic prostate cancer; Report from the 2017 Coffey‐Holden Prostate Cancer Academy Meeting

Abstract: This article reviews the presentations and discussions from the 2017 CHPCA Meeting in order to disseminate this knowledge and accelerate new biological understandings and advances in the treatment of patients with metastatic prostate cancer.

Cited by 11 publications

References 103 publications

A novel HDAC6 inhibitor interferes microtubule dynamics and spindle assembly checkpoint and sensitizes cisplatin‐induced apoptosis in castration‐resistant prostate cancer

A novel HDAC6 inhibitor interferes microtubule dynamics and spindle assembly checkpoint and sensitizes cisplatin‐induced apoptosis in castration‐resistant prostate cancer

Exploring new frontiers in prostate cancer research: Report from the 2022 Coffey−Holden prostate cancer academy meeting

Prostate cancer research in the 21st century; report from the 2021 Coffey‐Holden prostate cancer academy meeting

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