Epigenetic modulation of PTEN expression during antiandrogenic therapies in human prostate cancer

Gravina, Giovanni Luca; Biordi, Leda; Martella, Francesco; Flati, Vincenzo; Ricevuto, Enrico; Ficorella, Corrado; Tombolini, Vincenzo; Festuccia, Claudio

doi:10.3892/ijo_00000429

Cited by 4 publications

(1 citation statement)

References 34 publications

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“…However, several other mechanisms have also been reported, including inactivating somatic mutations (predominantly frameshift or non-sense truncating mutations), suppression of PTEN -targeting microRNAs (miRNAs) and inactivating post-translational modifications (e.g., phosphorylation and ubiquitylation) [ 7 , 8 , 9 , 10 , 11 ]. Infrequent epigenetic silencing via methylation of the PTEN promoter has also been observed in patients with prostate cancer [ 10 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

The PTEN Conundrum: How to Target PTEN-Deficient Prostate Cancer

Turnham

Bullock

Dass

et al. 2020

Cells

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Loss of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which negatively regulates the PI3K–AKT–mTOR pathway, is strongly linked to advanced prostate cancer progression and poor clinical outcome. Accordingly, several therapeutic approaches are currently being explored to combat PTEN-deficient tumors. These include classical inhibition of the PI3K–AKT–mTOR signaling network, as well as new approaches that restore PTEN function, or target PTEN regulation of chromosome stability, DNA damage repair and the tumor microenvironment. While targeting PTEN-deficient prostate cancer remains a clinical challenge, new advances in the field of precision medicine indicate that PTEN loss provides a valuable biomarker to stratify prostate cancer patients for treatments, which may improve overall outcome. Here, we discuss the clinical implications of PTEN loss in the management of prostate cancer and review recent therapeutic advances in targeting PTEN-deficient prostate cancer. Deepening our understanding of how PTEN loss contributes to prostate cancer growth and therapeutic resistance will inform the design of future clinical studies and precision-medicine strategies that will ultimately improve patient care.

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Section: Introductionmentioning

confidence: 99%

The PTEN Conundrum: How to Target PTEN-Deficient Prostate Cancer

Turnham

Bullock

Dass

et al. 2020

Cells

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At the Bench: Pre-clinical evidence for multiple functions of CXCR4 in cancer

Luker

Yang

Richmond

et al. 2020

Journal of Leukocyte Biology

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Signaling through chemokine receptor, C-X-C chemokine receptor type 4 (CXCR4) regulates essential processes in normal physiology, including embryogenesis, tissue repair, angiogenesis, and trafficking of immune cells. Tumors co-opt many of these fundamental processes to directly stimulate proliferation, invasion, and metastasis of cancer cells. CXCR4 signaling contributes to critical functions of stromal cells in cancer, including angiogenesis and multiple cell types in the tumor immune environment. Studies in animal models of several different types of cancers consistently demonstrate essential functions of CXCR4 in tumor initiation, local invasion, and metastasis to lymph nodes and distant organs. Data from animal models support clinical observations showing that integrated effects of CXCR4 on cancer and stromal cells correlate with metastasis and overall poor prognosis in >20 different human malignancies. Small molecules, Abs, and peptidic agents have shown anticancer efficacy in animal models, sparking ongoing efforts at clinical translation for cancer therapy. Investigators also are developing companion CXCR4-targeted imaging agents with potential to stratify patients for CXCR4-targeted therapy and monitor treatment efficacy. Here, pre-clinical studies demonstrating functions of CXCR4 in cancer are reviewed.

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Biological rationale for the use of DNA methyltransferase inhibitors as new strategy for modulation of tumor response to chemotherapy and radiation

et al. 2010

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Epigenetic modifications play a key role in the patho-physiology of many tumors and the current use of agents targeting epigenetic changes has become a topic of intense interest in cancer research. DNA methyltransferase (DNMT) inhibitors represent a promising class of epigenetic modulators. Research performed yielded promising anti-tumorigenic activity for these agents in vitro and in vivo against a variety of hematologic and solid tumors. These epigenetic modulators cause cell cycle and growth arrest, differentiation and apoptosis. Rationale for combining these agents with cytotoxic therapy or radiation is straightforward since the use of DNMT inhibitor offers greatly improved access for cytotoxic agents or radiation for targeting DNA-protein complex. The positive results obtained with these combined approaches in preclinical cancer models demonstrate the potential impact DNMT inhibitors may have in treatments of different cancer types. Therefore, as the emerging interest in use of DNMT inhibitors as a potential chemo- or radiation sensitizers is constantly increasing, further clinical investigations are inevitable in order to finalize and confirm the consistency of current observations.The present article will provide a brief review of the biological significance and rationale for the clinical potential of DNMT inhibitors in combination with other chemotherapeutics or ionizing radiation. The molecular basis and mechanisms of action for these combined treatments will be discussed herein.

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Epigenetic modulation of PTEN expression during antiandrogenic therapies in human prostate cancer

Cited by 4 publications

References 34 publications

The PTEN Conundrum: How to Target PTEN-Deficient Prostate Cancer

The PTEN Conundrum: How to Target PTEN-Deficient Prostate Cancer

At the Bench: Pre-clinical evidence for multiple functions of CXCR4 in cancer

Biological rationale for the use of DNA methyltransferase inhibitors as new strategy for modulation of tumor response to chemotherapy and radiation

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