Exploiting Epigenetic Alterations in Prostate Cancer

Baumgart, Simon J.; Haendler, Bernard

doi:10.3390/ijms18051017

Cited by 29 publications

(18 citation statements)

References 174 publications

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“…Molecular probes for different BRD targets are now being clinically tested in PC patients for exploiting epigenetic alterations (Fernandez-Salas et al 2016, Baumgart & Haendler 2017, Urbanucci & Mills 2018. Whether selection of patients with high chromatin deregulation will respond better to these therapeutic approaches/regimens remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Chromatin reprogramming as an adaptation mechanism in advanced prostate cancer

Braadland

Urbanucci

2019

Endocrine-Related Cancer

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Tumor evolution is based on the ability to constantly mutate and activate different pathways under the selective pressure of targeted therapies. Epigenetic alterations including those of the chromatin structure are associated with tumor initiation, progression and drug resistance. Many cancers, including prostate cancer, present enlarged nuclei, and chromatin appears altered and irregular. These phenotypic changes are likely to result from epigenetic dysregulation. High-throughput sequencing applied to bulk samples and now to single cells has made it possible to study these processes in unprecedented detail. It is therefore timely to review the impact of chromatin relaxation and increased DNA accessibility on prostate cancer growth and drug resistance, and their effects on gene expression. In particular, we focus on the contribution of chromatinassociated proteins such as the bromodomain-containing proteins to chromatin relaxation. We discuss the consequence of this for androgen receptor transcriptional activity and briefly summarize wider gain-of-function effects on other oncogenic transcription factors and implications for more effective prostate cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Chromatin reprogramming as an adaptation mechanism in advanced prostate cancer

Braadland

Urbanucci

2019

Endocrine-Related Cancer

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“…This was however not seen when using EZH2 inhibitors with another chemical scaffold [ 93 ]. EED is another core component of the PRC2 complex and its inhibitor MAK683, which is related to EED226 [ 94 ], has recently entered a clinical phase 1 study which includes prostate cancer patients [ 95 ].…”

Section: Treatment Options and Potential Novel Therapiesmentioning

confidence: 99%

“…Interestingly, resistance mechanisms to BET inhibitors linked to mutations in the speckle-type POZ protein (SPOP), a component of the cullin-RING-based E3 ubiquitin ligase complex, which result in BET protein stabilization, and to CDK9-mediated phosphorylation of AR, have been identified [ 111 , 112 , 113 ]. Clinical trials are ongoing in solid tumors for several BET inhibitors including MK-8628, ZEN003694, INCB057643 and ODM-207 [ 22 , 95 , 114 ].…”

Section: Treatment Options and Potential Novel Therapiesmentioning

confidence: 99%

Recent Advances in Prostate Cancer Treatment and Drug Discovery

Nevedomskaya

Baumgart

Haendler

2018

IJMS

Self Cite

198

174

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Novel drugs, drug sequences and combinations have improved the outcome of prostate cancer in recent years. The latest approvals include abiraterone acetate, enzalutamide and apalutamide which target androgen receptor (AR) signaling, radium-223 dichloride for reduction of bone metastases, sipuleucel-T immunotherapy and taxane-based chemotherapy. Adding abiraterone acetate to androgen deprivation therapy (ADT) in order to achieve complete androgen blockade has proven highly beneficial for treatment of locally advanced prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC). Also, ADT together with docetaxel treatment showed significant benefit in mHSPC. Ongoing clinical trials for different subgroups of prostate cancer patients include the evaluation of the second-generation AR antagonists enzalutamide, apalutamide and darolutamide, of inhibitors of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway, of inhibitors of DNA damage response, of targeted alpha therapy and of prostate-specific membrane antigen (PSMA) targeting approaches. Advanced clinical studies with immune checkpoint inhibitors have shown limited benefits in prostate cancer and more trials are needed to demonstrate efficacy. The identification of improved, personalized treatments will be much supported by the major progress recently made in the molecular characterization of early- and late-stage prostate cancer using “omics” technologies. This has already led to novel classifications of prostate tumors based on gene expression profiles and mutation status, and should greatly help in the choice of novel targeted therapies best tailored to the needs of patients.

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“…The epigenetic background of PCa is very diverse [130]. Several gene promoters are consistently found to be hypermethylated in PCa, including for instance GSTP1, which can be detected in several bodily fluids, including plasma or urine [131][132][133][134].…”

Section: Role Of Immunoepigenetics?mentioning

confidence: 99%

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Lobo

Jerónimo

Henrique

2020

IJMS

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In the last years, we have witnessed remarkable advances in targeted therapies for cancer patients. There is a growing effort to either replace or reduce the dose of unspecific, systemic (chemo)therapies, given the associated short- and long-term side effects, by introducing more specific targeted therapies as single or combination agents. Due to the well-known implications of the immune system and epigenetic landscape in modulating cancer development, both have been explored as potential targets in several malignancies, including those affecting the genitourinary tract. As the immune system function is also epigenetically regulated, there is rationale for combining both strategies. However, this is still rather underexplored, namely in urological tumors. We aim to briefly review the use of immune therapies in prostate, kidney, bladder, and testicular cancer, and further describe studies providing supporting evidence on their combination with epigenetic-based therapies.

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Exploiting Epigenetic Alterations in Prostate Cancer

Cited by 29 publications

References 174 publications

Chromatin reprogramming as an adaptation mechanism in advanced prostate cancer

Chromatin reprogramming as an adaptation mechanism in advanced prostate cancer

Recent Advances in Prostate Cancer Treatment and Drug Discovery

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

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