Advances in epigenetic therapeutics with focus on solid tumors

Jin, Ning; George, Tesmol G.; Otterson, Gregory A.; Verschraegen, Claire F.; Wen, Haitao; Carbone, David P.; Herman, James G.; Bertino, Erin M.; He, Kai

doi:10.1186/s13148-021-01069-7

Cited by 65 publications

(41 citation statements)

References 206 publications

(192 reference statements)

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“…Therefore, epi-drug development should follow a more personalized approach, with further identification of robust predictive biomarker selection and subsequent validation of this strategy in clinical studies [ 39 ]. Current literature highlights that, besides their use as monotherapy, epigenetic drugs may synergize with other anti-cancer compounds and reverse therapy resistance in both preclinical and clinical settings [ 236 ]. The administration of certain epigenetic drugs before chemotherapy or targeted therapy can be used for priming cancer cells to be more sensitive to these approaches, as epigenetic drugs can induce chromatin decompaction, making it more accessible to antineoplastic compounds [ 203 ].…”

Section: Discussionmentioning

confidence: 99%

“…The low efficacy of epi-therapies in solid tumors compared to blood cancers is still poorly understood. One possible explanation may be that these agents reach their therapeutic concentrations more efficiently in blood cancers so that their short life may not affect their activities as it may do in solid tumors [ 236 ]. Another explanation refers to the fact that solid and hematological tumors differ considerably in terms of cell differentiation and epigenetic plasticity, with solid tumors originating from a more terminally differentiated state that is much more difficult to be transcriptomically reprogrammed [ 39 ].…”

Section: Epigenetics-based Therapies For CMmentioning

confidence: 99%

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Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma

Dobre

Constantin

Costache

et al. 2021

JPM

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Epigenetic alterations have emerged as essential contributors in the pathogenesis of various human diseases, including cutaneous melanoma (CM). Unlike genetic changes, epigenetic modifications are highly dynamic and reversible and thus easy to regulate. Here, we present a comprehensive review of the latest research findings on the role of genetic and epigenetic alterations in CM initiation and development. We believe that a better understanding of how aberrant DNA methylation and histone modifications, along with other molecular processes, affect the genesis and clinical behavior of CM can provide the clinical management of this disease a wide range of diagnostic and prognostic biomarkers, as well as potential therapeutic targets that can be used to prevent or abrogate drug resistance. We will also approach the modalities by which these epigenetic alterations can be used to customize the therapeutic algorithms in CM, the current status of epi-therapies, and the preliminary results of epigenetic and traditional combinatorial pharmacological approaches in this fatal disease.

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Section: Discussionmentioning

confidence: 99%

Section: Epigenetics-based Therapies For CMmentioning

confidence: 99%

Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma

Dobre

Constantin

Costache

et al. 2021

JPM

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“…Changes in the epigenetic factors lead to alterations in the expression of key oncogenes and TSGs [17]. Several epigenetic processes in lung cancer have an impact on cancer hallmarks, such as proliferation, invasion, metastasis, apoptosis, and regulations of cell cycle [18]. Further to cancer hallmarks, epigenetic deregulation in lung cancer affects numerous impactful signalling pathways, including the ERK family, NF-kB signalling pathway, and Hedgehog signalling pathway [17].…”

Section: Epigenetics In Lung Cancermentioning

confidence: 99%

Histone Modification in NSCLC: Molecular Mechanisms and Therapeutic Targets

Bajbouj

Al-Ali

Ramakrishnan

et al. 2021

IJMS

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Lung cancer is the leading cause of cancer mortality in both genders, with non-small cell lung cancer (NSCLC) accounting for about 85% of all lung cancers. At the time of diagnosis, the tumour is usually locally advanced or metastatic, shaping a poor disease outcome. NSCLC includes adenocarcinoma, squamous cell carcinoma, and large cell lung carcinoma. Searching for novel therapeutic targets is mandated due to the modest effect of platinum-based therapy as well as the targeted therapies developed in the last decade. The latter is mainly due to the lack of mutation detection in around half of all NSCLC cases. New therapeutic modalities are also required to enhance the effect of immunotherapy in NSCLC. Identifying the molecular signature of NSCLC subtypes, including genetics and epigenetic variation, is crucial for selecting the appropriate therapy or combination of therapies. Epigenetic dysregulation has a key role in the tumourigenicity, tumour heterogeneity, and tumour resistance to conventional anti-cancer therapy. Epigenomic modulation is a potential therapeutic strategy in NSCLC that was suggested a long time ago and recently starting to attract further attention. Histone acetylation and deacetylation are the most frequently studied patterns of epigenetic modification. Several histone deacetylase (HDAC) inhibitors (HDIs), such as vorinostat and panobinostat, have shown promise in preclinical and clinical investigations on NSCLC. However, further research on HDIs in NSCLC is needed to assess their anti-tumour impact. Another modification, histone methylation, is one of the most well recognized patterns of histone modification. It can either promote or inhibit transcription at different gene loci, thus playing a rather complex role in lung cancer. Some histone methylation modifiers have demonstrated altered activities, suggesting their oncogenic or tumour-suppressive roles. In this review, patterns of histone modifications in NSCLC will be discussed, focusing on the molecular mechanisms of epigenetic modifications in tumour progression and metastasis, as well as in developing drug resistance. Then, we will explore the therapeutic targets emerging from studying the NSCLC epigenome, referring to the completed and ongoing clinical trials on those medications.

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“…Changes in epigenetic profiles at the cell or organismal level are among the most common molecular alterations in virtually all complex diseases, and may underlie both causal associations as well as constitute epiphenomena. Alterations of DNA methylation profiles have been recognized as an important, and in many cases essential, line of research to understand the pathophysiology of the specific condition of interest, as well as to develop diagnostic methods and therapeutic applications in cancer [ 3 , 4 , 5 ], diabetes [ 6 ], metabolic syndrome [ 7 ], atherosclerosis [ 8 ], inflammatory bowel disease [ 9 ], autoimmune diseases [ 10 ], psychiatric disorders [ 11 ], and neurodegenerative disorders [ 12 ]. As such, extrapolation of this extensive line of evidence to sleep disorders should not be viewed as particularly surprising.…”

Section: The Role Of Epigenetics In Complex Pathologiesmentioning

confidence: 99%