Androgen Receptor Signaling Inhibition in Advanced Castration Resistance Prostate Cancer: What Is Expected for the Near Future?

Pozas, Javier; Rodríguez, Sara Álvarez; Albarrán, Víctor; Burgos, Javier; Santoni, Matteo; Kopp, Ray Manneh; Molina‐Cerrillo, Javier; Alonso‐Gordoa, Teresa

doi:10.3390/cancers14246071

Cited by 9 publications

(23 citation statements)

References 165 publications

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“…Coregulators include coactivators and corepressors, with increased activity of coactivators and reduced influence of corepressors contributing to the promotion of castration resistance. 45 For example, FKBP51 forms a super-chaperone complex and stimulates androgen binding. The SRC family (SRC1, SRC2, and SRC3) and histone acetyltransferase proteins, such as CBP, p300, and galectin-3, enhance AR activation, augmenting the expression of specific AR target genes.…”

Section: Ar Signaling Pathway and Mechanisms Of Treatment Resistancementioning

confidence: 99%

“…The SRC family (SRC1, SRC2, and SRC3) and histone acetyltransferase proteins, such as CBP, p300, and galectin-3, enhance AR activation, augmenting the expression of specific AR target genes. 45 These coregulators play crucial roles in AR activation during prostate cancer progression. SPOP, an important tumor suppressor, promotes SRC-3 protein degradation, subsequently inhibiting AR transcriptional activity.…”

Section: Ar Signaling Pathway and Mechanisms Of Treatment Resistancementioning

confidence: 99%

“…In prostate cancer, AR‐related coregulators and TFs are known to shift according to the disease stage, selectively expressing AR‐responsive genes. Coregulators include co‐activators and corepressors, with increased activity of co‐activators and reduced influence of corepressors contributing to the promotion of castration resistance 45 . For example, FKBP51 forms a super‐chaperone complex and stimulates androgen binding.…”

Section: Ar Signaling Pathway and Mechanisms Of Treatment Resistancementioning

confidence: 99%

See 2 more Smart Citations

Exploring androgen receptor signaling pathway in prostate cancer: A path to new discoveries

Obinata,

Takayama,

Inoue

et al. 2024

Int J of Urology

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Androgen deprivation therapy has achieved significant success in treating prostate cancer through strategies centered on the androgen receptor. However, the emergence of castration‐resistant prostate cancer highlights this therapy limitation, underscoring the need to elucidate the mechanisms of treatment resistance. This review aimed to focus on multifaceted resistance mechanisms, including androgen receptor overexpression, splice variants, missense mutations, the involvement of the glucocorticoid receptor, and alterations in coregulators and transcription factors, revealing their roles in castration‐resistant prostate cancer progression. These mechanisms promote cell survival and proliferation, depending on the androgen receptor signaling pathway, leading to resistance to conventional therapies. Amplification and mutations in the androgen receptor gene facilitate selective adaptation in treatment‐resistant cells, consequently diminishing therapeutic efficacy. Furthermore, the activation of glucocorticoid receptors and aberrant regulation of specific coregulators and transcription factors contribute to the activation of androgen receptor‐independent signaling pathways, promoting cell survival and proliferation. These findings hold promise for identifying new targets for treating castration‐resistant prostate cancer and developing personalized treatment strategies. The development of future therapies will hinge on precisely targeting the androgen receptor signaling pathway, necessitating a deeper understanding of the molecular targets unique to castration‐resistant prostate cancer.

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Section: Ar Signaling Pathway and Mechanisms Of Treatment Resistancementioning

confidence: 99%

Section: Ar Signaling Pathway and Mechanisms Of Treatment Resistancementioning

confidence: 99%

Section: Ar Signaling Pathway and Mechanisms Of Treatment Resistancementioning

confidence: 99%

See 1 more Smart Citation

Exploring androgen receptor signaling pathway in prostate cancer: A path to new discoveries

Obinata,

Takayama,

Inoue

et al. 2024

Int J of Urology

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“…Another way to stimulate cell signaling has also been described and its name is “non-genomic signaling”. The latter is mediated by cytoplasmic AR, which facilitates the activation of kinase-signaling cascades, including the Ras-Raf-1, (PI3K)/Akt and protein kinase C (PKC), which, in turn, converge on the mitogen-activated protein kinase (MAPK) pathway, leading in this way to cell proliferation [ 60 , 61 ]. Figure 4 illustrates the AR mediated intracellular pathway, highlighting its importance in SDC carcinogenesis.…”

Section: Salivary Duct Carcinoma (Sdc)mentioning

confidence: 99%

Translational Insights in the Landscape of Salivary Gland Cancers: Ready for a New Era?

Perri,

Fusco,

Sabbatino

et al. 2024

Cancers

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Salivary gland carcinomas (SGCs) are rare neoplasms, representing less than 10% of all head and neck tumors, but they are extremely heterogeneous from the histological point of view, their clinical behavior, and their genetics. The guidelines regarding their treatment include surgery in most cases, which can also play an important role in oligometastatic disease. Where surgery cannot be used, systemic therapy comes into play. Systemic therapy for many years has been represented by polychemotherapy, but recently, with the affirmation of translational research, it can also count on targeted therapy, at least in some subtypes of SGCs. Interestingly, in some SGC histotypes, predominant mutations have been identified, which in some cases behave as “driver mutations”, namely mutations capable of governing the carcinogenesis process. Targeting these driver mutations may be an effective therapeutic strategy. Nonetheless, it is not always possible to have drugs suitable for targeting driver mutations—and targeting driver mutations is not always accompanied by a clinical benefit. In this review, we will analyze the main mutations predominant in the various histotypes of SGCs.

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“…The introduction of a new concept of systemic disease: high-risk or high-volume vs. low-risk and low-volume disease [119] opened a new clinical scenario for sequence therapies using the above-discussed drugs [120,121]. All major clinical associations have reflected these breakthroughs in treatment in updated professional guidelines.…”

Section: Clinical Management Of Prostate Cancermentioning

confidence: 99%

Advances in Molecular Regulation of Prostate Cancer Cells by Top Natural Products of Malaysia

Prieto

Hanafi

2023

CIMB

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Prostate cancer (PCa) remains both a global health burden and a scientific challenge. We present a review of the molecular targets driving current drug discovery to fight this disease. Moreover, the preventable nature of most PCa cases represents an opportunity for phytochemicals as chemopreventive when adequately integrated into nutritional interventions. With a renovated interest in natural remedies as a commodity and their essential role in cancer drug discovery, Malaysia is looking towards capitalizing on its mega biodiversity, which includes the oldest rainforest in the world and an estimated 1200 medicinal plants. We here explore whether the list of top Malay plants prioritized by the Malaysian government may fulfill the potential of becoming newer, sustainable sources of prostate cancer chemotherapy. These include Andrographis paniculate, Centella asiatica, Clinacanthus nutans, Eurycoma longifolia, Ficus deltoidea, Hibiscus sabdariffa, Marantodes pumilum (syn. Labisia pumila), Morinda citrifolia, Orthosiphon aristatus, and Phyllanthus niruri. Our review highlights the importance of resistance factors such as Smac/DIABLO in cancer progression, the role of the CXCL12/CXCR4 axis in cancer metastasis, and the regulation of PCa cells by some promising terpenes (andrographolide, Asiatic acid, rosmarinic acid), flavonoids (isovitexin, gossypin, sinensetin), and alkylresorcinols (labisiaquinones) among others.

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Androgen Receptor Signaling Inhibition in Advanced Castration Resistance Prostate Cancer: What Is Expected for the Near Future?

Cited by 9 publications

References 165 publications

Exploring androgen receptor signaling pathway in prostate cancer: A path to new discoveries

Exploring androgen receptor signaling pathway in prostate cancer: A path to new discoveries

Translational Insights in the Landscape of Salivary Gland Cancers: Ready for a New Era?

Advances in Molecular Regulation of Prostate Cancer Cells by Top Natural Products of Malaysia

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