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

Katleba, Kimberley D.; Ghosh, Paramita M.; Mudryj, Maria

doi:10.3390/biomedicines11082215

Cited by 4 publications

(3 citation statements)

References 254 publications

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“…However, a portion of HCC was detected with the expression of C-terminal truncated AR-SVs. AR-SVs have been identified to play an important role in the acquired resistance to AR inhibitors (Dauki et al, 2020;Qiao et al, 2021;Katleba et al, 2023). Therefore, we imply that AR-SVs might also be involved in the occurrence of acquired resistance to AR inhibitors in HCC.…”

Section: Discussionmentioning

confidence: 78%

Exploiting gender-based biomarkers and drug targets: advancing personalized therapeutic strategies in hepatocellular carcinoma

Su,

Luo,

Yan

et al. 2024

Front. Pharmacol.

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This review systematically examines gender differences in hepatocellular carcinoma (HCC), identifying the influence of sex hormones, genetic variance, and environmental factors on the disease’s epidemiology and treatment outcomes. Recognizing the liver as a sexually dimorphic organ, we highlight how gender-specific risk factors, such as alcohol consumption and obesity, contribute differently to hepatocarcinogenesis in men and women. We explore molecular mechanisms, including the differential expression of androgen and estrogen receptors, which mediate diverse pathways in tumor biology such as cell proliferation, apoptosis, and DNA repair. Our analysis underscores the critical need for gender-specific research in liver cancer, from molecular studies to clinical trials, to improve diagnostic accuracy and therapeutic effectiveness. By incorporating a gender perspective into all facets of liver cancer research, we advocate for a more precise and personalized approach to cancer treatment that acknowledges gender as a significant factor in both the progression of HCC and its response to treatment. This review aims to foster a deeper understanding of the biological and molecular bases of gender differences in HCC and to promote the development of tailored interventions that enhance outcomes for all patients.

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Section: Discussionmentioning

confidence: 78%

Exploiting gender-based biomarkers and drug targets: advancing personalized therapeutic strategies in hepatocellular carcinoma

Su,

Luo,

Yan

et al. 2024

Front. Pharmacol.

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“…Moreover, the proliferative advantage of spheroids could possibly be driven by AR- splice variants, such as AR-V7, which elevate the expression of AR responsive genes promoting tumor initiation and progression by ligand-independent AR pathway activation 23 .…”

Section: Discussionmentioning

confidence: 99%

Tumor promoting effect of spheroids in an orthotopic prostate cancer mouse model

Bastian,

Zeuschner,

Stöckle

et al. 2024

Sci Rep

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In this study, we aimed to establish a technique for intraprostatic implantation of prostate cancer (PCa) spheroids and to identify the impact of three-dimensional organization of PCa cells on tumor progression and metastasis in a representative in vivo model. 40,000 LNCaP cells were implanted into the prostate of immunodeficient SCID mice either as single cells (n = 8) or as preformed 3D spheroids (n = 8). For a follow up of 20 weeks, tumor growth was monitored by serum PSA and high-resolution 3D ultrasonography. Eventually, animals were sacrificed and autopsied. The organ dissects were analyzed for the presence of metastases by histology (H&E) and immunohistochemistry (AMACR, AR, Ki-67, CK5, CK8, E-Cadherin, Vimentin). Solid intraprostatic tumors developed in 50% of mice after spheroid implantation and in 50% of mice after implantation of a single cells. Primary tumors of LNCaP spheroids evolved earlier, exhibiting a shorter tumor doubling time whilst developing larger tumor volumes, which was reflected by a higher immunohistochemical expression of Ki-67 and AR, too. Spheroid tumors established lung and lymph node metastases in 75% of mice, in contrast to 50% of mice after single cell implantation. Our technique enables a variety of studies regarding the influence of the tumor microenvironment on PCa progression.

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“…About 20 AR-Vs have been identified. Almost all of the subsequently discovered AR-Vs have an NTD and DBD but lack an LBD in full or in part [8,36]. The lack of LBDs in constitutively active AR-Vs is one of the resistant mechanisms underlying the current therapies that target AR signaling pathways [37].…”

Section: Ar Splice Variants (Ar-vs)mentioning

confidence: 99%

Treatments Targeting the Androgen Receptor and Its Splice Variants in Breast Cancer

Tien,

Sadar

2024

IJMS

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Breast cancer is a major cause of death worldwide. The complexity of endocrine regulation in breast cancer may allow the cancer cells to escape from a particular treatment and result in resistant and aggressive disease. These breast cancers usually have fewer treatment options. Targeted therapies for cancer patients may offer fewer adverse side effects because of specificity compared to conventional chemotherapy. Signaling pathways of nuclear receptors, such as the estrogen receptor (ER), have been intensively studied and used as therapeutic targets. Recently, the role of the androgen receptor (AR) in breast cancer is gaining greater attention as a therapeutic target and as a prognostic biomarker. The expression of constitutively active truncated AR splice variants in breast cancer is a possible mechanism contributing to treatment resistance. Therefore, targeting both the full-length AR and AR variants, either through the activation or suppression of AR function, depending on the status of the ER, progesterone receptor, or human epidermal growth factor receptor 2, may provide additional treatment options. Studies targeting AR in combination with other treatment strategies are ongoing in clinical trials. The determination of the status of nuclear receptors to classify and identify patient subgroups will facilitate optimized and targeted combination therapies.

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

Cited by 4 publications

References 254 publications

Exploiting gender-based biomarkers and drug targets: advancing personalized therapeutic strategies in hepatocellular carcinoma

Exploiting gender-based biomarkers and drug targets: advancing personalized therapeutic strategies in hepatocellular carcinoma

Tumor promoting effect of spheroids in an orthotopic prostate cancer mouse model

Treatments Targeting the Androgen Receptor and Its Splice Variants in Breast Cancer

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