Androgen receptor-dependent regulation of metabolism in high grade bladder cancer cells

Katleba, Kimberley D.; Tsamouri, Maria-Malvina; Jathal, Maitreyee K.; Baek, Han Bit; Armenta, Rebecca B.; Tepper, Clifford G.; Cortopassi, Gino A; Ghosh, Paramita M.; Mudryj, Maria

doi:10.1038/s41598-023-28692-z

Cited by 2 publications

(3 citation statements)

References 62 publications

(70 reference statements)

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“…At the present, metastatic castration‐resistant prostate cancer (mCRPC) remains incurable and fatal. AR antagonists are effective for the treatment of mCRPC, significantly improves the survival of prostate cancer patients with well tolerance 156,157 . A plenty of AR antagonists have been developed for the treatment of advanced prostate cancer, exemplified by enzalutamide.…”

Section: Vhl Ligands and Their Utilizations In Protacs For Cancer Dru...mentioning

confidence: 99%

“…AR antagonists are effective for the treatment of mCRPC, significantly improves the survival of prostate cancer patients with well tolerance. 156 , 157 A plenty of AR antagonists have been developed for the treatment of advanced prostate cancer, exemplified by enzalutamide. In prostate cancer patients, resistance to enzalutamide usually appears within 18 months.…”

Section: Vhl Ligands and Their Utilizations In Protacs For Cancer Dru...mentioning

confidence: 99%

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PROTACs: A novel strategy for cancer drug discovery and development

Han

Sun

2023

MedComm

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Proteolysis targeting chimera (PROTAC) technology has become a powerful strategy in drug discovery, especially for undruggable targets/proteins. A typical PROTAC degrader consists of three components: a small molecule that binds to a target protein, an E3 ligase ligand (consisting of an E3 ligase and its small molecule recruiter), and a chemical linker that hooks first two components together. In the past 20 years, we have witnessed advancement of multiple PRO-TAC degraders into the clinical trials for anticancer therapies. However, one of the major challenges of PROTAC technology is that only very limited number of E3 ligase recruiters are currently available as E3 ligand for targeted protein degradation (TPD), although human genome encodes more than 600 E3 ligases. Thus, there is an urgent need to identify additional effective E3 ligase recruiters for TPD applications. In this review, we summarized the existing RING-type E3 ubiquitin ligase and their small molecule recruiters that act as effective E3 ligands of PRO-TAC degraders and their application in anticancer drug discovery. We believe that this review could serve as a reference in future development of efficient E3 ligands of PROTAC technology for cancer drug discovery and development.

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Section: Vhl Ligands and Their Utilizations In Protacs For Cancer Dru...mentioning

confidence: 99%

Section: Vhl Ligands and Their Utilizations In Protacs For Cancer Dru...mentioning

confidence: 99%

PROTACs: A novel strategy for cancer drug discovery and development

Han

Sun

2023

MedComm

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“…Overexpression of FL-AR does not alter AR-SV expression, and conversely, overexpression of V19 does not reduce FL-AR; therefore, the reciprocal negative regulation observed in PCa is not apparent in BlCa. Transcript analysis following depletion of FL-AR, AR-V19, or total AR identified distinct but partly overlapping transcriptomes [ 164 ]. mTOR is decreased by deletion of Fl-AR, AR-V19, or all AR isoforms, and this is coupled with altered mTOR downstream signaling.…”

Section: Androgen Receptor Splice Variants In Human Malignanciesmentioning

confidence: 99%

Beyond Prostate Cancer: An Androgen Receptor Splice Variant Expression in Multiple Malignancies, Non-Cancer Pathologies, and Development

2023

Self Cite

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Multiple studies have demonstrated the importance of androgen receptor (AR) splice variants (SVs) in the progression of prostate cancer to the castration-resistant phenotype and their utility as a diagnostic. However, studies on AR expression in non-prostatic malignancies uncovered that AR-SVs are expressed in glioblastoma, breast, salivary, bladder, kidney, and liver cancers, where they have diverse roles in tumorigenesis. AR-SVs also have roles in non-cancer pathologies. In granulosa cells from women with polycystic ovarian syndrome, unique AR-SVs lead to an increase in androgen production. In patients with nonobstructive azoospermia, testicular Sertoli cells exhibit differential expression of AR-SVs, which is associated with impaired spermatogenesis. Moreover, AR-SVs have been identified in normal cells, including blood mononuclear cells, neuronal lipid rafts, and the placenta. The detection and characterization of AR-SVs in mammalian and non-mammalian species argue that AR-SV expression is evolutionarily conserved and that AR-SV-dependent signaling is a fundamental regulatory feature in multiple cellular contexts. These discoveries argue that alternative splicing of the AR transcript is a commonly used mechanism that leads to an expansion in the repertoire of signaling molecules needed in certain tissues. Various malignancies appropriate this mechanism of alternative AR splicing to acquire a proliferative and survival advantage.

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Androgen receptor-dependent regulation of metabolism in high grade bladder cancer cells

Cited by 2 publications

References 62 publications

PROTACs: A novel strategy for cancer drug discovery and development

PROTACs: A novel strategy for cancer drug discovery and development

Beyond Prostate Cancer: An Androgen Receptor Splice Variant Expression in Multiple Malignancies, Non-Cancer Pathologies, and Development

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