New therapeutic avenue of epigenetic modulations in cancer

Pan, Desi; Lu, Xianping

doi:10.21037/tbcr.2020.03.03

Cited by 3 publications

(4 citation statements)

References 21 publications

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“…Moreover, more than 10 other HDAC inhibitors have undergone or are undergoing clinical trials as monotherapy or in combination therapy in patients with hematologic malignancies or solid tumors. 452,453 For example, the benzamide inhibitor entinostat is currently assessed in phase III trials (NCT02115282 and NCT03538171) for the clinical benefit in patients with HR-positive, HER2-negative, locally advanced, or metastatic breast cancer. A phase I doseescalation multicentre trial (NCT00741234) demonstrated that the hydroxamate HDAC inhibitor pracinostat was safe, with modest single-agent activity in patients with advanced hematological malignancies.…”

Section: Ezh2 Inhibitorsmentioning

confidence: 99%

“…452,456,457 Furthermore, some novel combination strategies, such as combining HDAC inhibitors with epigenetic-targeted drugs, proteasome inhibitors, or immunotherapy, have also exhibited good therapeutic effects in preclinical studies. 453,[458][459][460] IDH1/2 inhibitors Isocitrate dehydrogenases (IDHs) include three subtypes (IDH1, IDH2, and IDH3) and are key enzymes that catalyze the conversion Fig. 3 Commonly altered epigenetic regulatory proteins implicated in cancer.…”

Section: Ezh2 Inhibitorsmentioning

confidence: 99%

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Small molecules in targeted cancer therapy: advances, challenges, and future perspectives

Zhong

Xiong

et al. 2021

Sig Transduct Target Ther

877

490

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Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-molecule targeted anti-cancer drugs still face many challenges, such as a low response rate and drug resistance. To better promote the development of targeted anti-cancer drugs, we conducted a comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification. We present all the approved drugs as well as important drug candidates in clinical trials for each target, discuss the current challenges, and provide insights and perspectives for the research and development of anti-cancer drugs.

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Section: Ezh2 Inhibitorsmentioning

confidence: 99%

Section: Ezh2 Inhibitorsmentioning

confidence: 99%

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives

Zhong

Xiong

et al. 2021

Sig Transduct Target Ther

877

490

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“…Despite both being benzamide HDACi differentially selective to class I HDACs 1, 2, and 3, the failure of entinostat's phase-III trial can be attributed to tucidinostat's ability to also inhibit class IIb isotype HDAC-10. In addition, tucidinostat deploys epigenetic modulation over tumor cells by archiving optimal blood concentration yielding an enhanced antitumor response (140). This provides evidence for the need for an HDACi to specifically inhibit HDAC-10 to enhance PFS and OS, a correlation previously conjected for other cancer types (141).…”

Section: Clinical Translation Of Targeted Hdaci Therapy Against Breast Cancermentioning

confidence: 82%

Rational Design and Development of HDAC Inhibitors for Breast Cancer Treatment

Mody

Bouckaert

Savvides

et al. 2021

CPD

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Background: Breast cancer is the most prevalent cancer amongst females across the globe and with over 2 million new cases reported in 2018, it poses huge economic burden to the already dwindling public health. A dearth of therapies in the pipeline to treat triple-negative breast cancers, and acquisition of resistance against existing line of treatments urges the need to strategize novel therapeutics in order to add new drugs to the pipeline. HDAC inhibitors (HDACi) is one such class of small molecule inhibitors that target histone deacetylases to bring about chromosomal remodelling and normalize dysregulated gene expression that marks breast cancer progression. Objective: While four HDACi have been approved by the FDA for treatment of different cancer types, no HDACi is specifically earmarked for clinical management of breast cancer. Owing to the differential HDAC expression pertaining to different types of breast cancers, isoform-selective HDAC inhibitors need to be discovered. Conclusion: This review attempts to set the stage for rational structure-based discovery of isoform-selective HDACi by providing structural insights into different HDACs and their catalytic folds based on their classes and individual landscape. Development of inhibitors in accordance with the differential expression of HDAC isoforms exhibited in breast cancer cells is a promising strategy to rationally design selective and effective inhibitors, adopting a ‘personalized-medicine’ approach.

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“…It has been suggested that Sirt inhibitors might be beneficial in the treatment of cancer; however, none of these inhibitors have been authorized for use in clinical practice as yet. Additionally, approximately 10 other HDAC inhibitors have completed or are conducting clinical studies as monotherapy or in combination treatment for patients with solid tumors or hematologic malignancies [ 15 ]. For instance, phase III studies (NCT02115282 and NCT03538171) are now evaluating the therapeutic benefit of the benzamide inhibitor entinostat in patients with HR-positive, HER2-negative, locally progressed, or metastatic breast cancer.…”

Section: Epidrugs: Toward Epigenetic Regulation Of Antitumor Immunitymentioning

confidence: 99%

What nature has to offer: Opportunities for immuno-oncology

Kousar¹,

Lin²,

Patrick³

et al. 2023

Journal of Food and Drug Analysis

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Recent rapid development of cancer therapy has come about with the paradigm shift from the traditional goal of targeting cancer cells themselves, to reprograming the immune tumor microenvironment. Accumulating evidence shows that compounds that target epigenetic regulation, called epidrugs, play a crucial role in mediating the immunogenicity of cancer cells and in reshaping antitumor immunity. A large body of literature has recognized natural compounds as epigenetic modulators for their immunomodulatory effects and anticancer potential. Unifying our understanding of the role of these biologically active compounds in immuno-oncology may open new avenues for more effective cancer therapies. In this review, we explore how natural compounds modulate the epigenetic machinery to shape antitumor immune response, highlighting the promise offered by the Mother Nature that could be exploited therapeutically to improve outcomes for cancer patients.

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New therapeutic avenue of epigenetic modulations in cancer

Cited by 3 publications

References 21 publications

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives

Small molecules in targeted cancer therapy: advances, challenges, and future perspectives

Rational Design and Development of HDAC Inhibitors for Breast Cancer Treatment

What nature has to offer: Opportunities for immuno-oncology

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