Phase I/II Study of Azacitidine, Docetaxel, and Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Therapy

Singal, Rakesh; Ramachandran, K.; Gordián, Edna; Quintero, Carlos; Zhao, Wei; Reis, Isildinha M.

doi:10.1016/j.clgc.2014.07.008

Cited by 62 publications

(55 citation statements)

References 18 publications

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“…Additionally, 5-azacytidine has shown some promising results in a phase II clinical trial for metastatic PCa with demonstrated clinical resistance to docetaxel. In this study, a majority of patients demonstrated a decrease in PSA levels after 12 weeks of therapy (186) .…”

Section: Introductionmentioning

confidence: 66%

Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer

Foley

Mitsiades

2016

HORM CANC

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Medical or surgical castration serve as the backbone of systemic therapy for advanced and metastatic prostate cancer, taking advantage of the importance of androgen signaling in this disease. Unfortunately, resistance to castration emerges almost universally. Despite the development and approval of new and more potent androgen synthesis inhibitors and androgen receptor (AR) antagonists, prostate cancers continue to develop resistance to these therapeutics, while often maintaining their dependence on the AR signaling axis. This highlights the need for innovative therapeutic approaches that aim to continue disrupting AR downstream signaling, but are orthogonal to directly targeting the AR itself. In this review, we discuss the preclinical research that has been done, as well as clinical trials for prostate cancer, on inhibiting several important families of AR interacting proteins, including chaperones (such as HSP90 and FKBP52), pioneer factors (including FOXA1 and GATA-2), and AR transcriptional coregulators such as the p160 steroid receptor coactivators (SRCs) SRC-1, SRC-2, SRC-3, as well as lysine deacetylases (KDACs) and lysine acetyltransferases (KATs). Researching the effect of, and developing new therapeutic agents that target, the AR signaling axis is critical to advancing our understanding of prostate cancer biology, and to continuing to improve treatments for prostate cancer and for overcoming castration-resistance.

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Section: Introductionmentioning

confidence: 66%

Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer

Foley

Mitsiades

2016

HORM CANC

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“…5′Azacitidine is a DNA methyltransferase inhibitor that is commonly used to treat myelodysplastic syndromes [242]. Importantly, epigenetic alterations, including DNA methylation, have been found to play an important role in therapy resistance, and 5′Azacitidine, and other demethylating agents, have been shown to be effective in combination therapy to improve chemosensitivity in other cancer types [243,244,245,246,247,248]. In PCa, for example, 5′Azacitidine improved chemosensitivity to docetaxel in patients with metastatic CRPC in phase I/II clinical trials [248].…”

Section: Therapeutic Approaches To Prostate Cancer: Targeting the mentioning

confidence: 99%

One-Carbon Metabolism in Prostate Cancer: The Role of Androgen Signaling

Corbin

Ruiz-Echevarría

2016

IJMS

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Cancer cell metabolism differs significantly from the metabolism of non-transformed cells. This altered metabolic reprogramming mediates changes in the uptake and use of nutrients that permit high rates of proliferation, growth, and survival. The androgen receptor (AR) plays an essential role in the establishment and progression of prostate cancer (PCa), and in the metabolic adaptation that takes place during this progression. In its role as a transcription factor, the AR directly affects the expression of several effectors and regulators of essential catabolic and biosynthetic pathways. Indirectly, as a modulator of the one-carbon metabolism, the AR can affect epigenetic processes, DNA metabolism, and redox balance, all of which are important factors in tumorigenesis. In this review, we focus on the role of AR-signaling on one-carbon metabolism in tumorigenesis. Clinical implications of one-carbon metabolism and AR-targeted therapies for PCa are discussed in this context.

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“…Presently, azacitidine is being evaluated in three clinical studies for prostate cancer treatment. In the most advanced one, it is tested in combination with docetaxel in chemotherapy-resistant metastatic CRPC patients to determine whether their response to docetaxel can be restored [154]. Phase 2 results show an objective response in three out of ten patients but more studies are needed to confirm this.…”

Section: Clinical Studies In Prostate Cancer Addressing Epigeneticmentioning

confidence: 99%

Exploiting Epigenetic Alterations in Prostate Cancer

Baumgart

Haendler

2017

IJMS

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Prostate cancer affects an increasing number of men worldwide and is a leading cause of cancer-associated deaths. Beside genetic mutations, many epigenetic alterations including DNA and histone modifications have been identified in clinical prostate tumor samples. They have been linked to aberrant activity of enzymes and reader proteins involved in these epigenetic processes, leading to the search for dedicated inhibitory compounds. In the wake of encouraging anti-tumor efficacy results in preclinical models, epigenetic modulators addressing different targets are now being tested in prostate cancer patients. In addition, the assessment of microRNAs as stratification biomarkers, and early clinical trials evaluating suppressor microRNAs as potential prostate cancer treatment are being discussed.

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Phase I/II Study of Azacitidine, Docetaxel, and Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Therapy

Cited by 62 publications

References 18 publications

Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer

Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer

One-Carbon Metabolism in Prostate Cancer: The Role of Androgen Signaling

Exploiting Epigenetic Alterations in Prostate Cancer

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