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Review
. 2020 Sep 11:11:578011.
doi: 10.3389/fgene.2020.578011. eCollection 2020.

Synergistic Enhancement of Cancer Therapy Using HDAC Inhibitors: Opportunity for Clinical Trials

Lourdes Hontecillas-Prieto  1 , Rocío Flores-Campos  1 , Andrew Silver  2 , Enrique de Álava  1   3 , Nabil Hajji  4 , Daniel J García-Domínguez  1
Affiliations
Review

Synergistic Enhancement of Cancer Therapy Using HDAC Inhibitors: Opportunity for Clinical Trials

Lourdes Hontecillas-Prieto et al. Front Genet. .

Abstract

Chemotherapy is one of the most established and effective treatments for almost all types of cancer. However, the elevated toxicity due to the non-tumor-associated effects, development of secondary malignancies, infertility, radiation-induced fibrosis and resistance to treatment limit the effectiveness and safety of treatment. In addition, these multiple factors significantly impact quality of life. Over the last decades, our increased understanding of cancer epigenetics has led to new therapeutic approaches and the promise of improved patient outcomes. Epigenetic alterations are commonly found in cancer, especially the increased expression and activity of histone deacetylases (HDACs). Dysregulation of HDACs are critical to the development and progression of the majority of tumors. Hence, HDACs inhibitors (HDACis) were developed and now represent a very promising treatment strategy. The use of HDACis as monotherapy has shown very positive pre-clinical results, but clinical trials have had only limited success. However, combinatorial regimens with other cancer drugs have shown synergistic effects both in pre-clinical and clinical studies. At the same time, these combinations have enhanced the efficacy, reduced the toxicity and tumor resistance to therapy. In this review, we will examine examples of HDACis used in combination with other cancer drugs and highlight the synergistic effects observed in recent preclinical and clinical studies.

Keywords: HDAC inhibitors (HDACis); cancer; clinical trials; combination treatment; histone deacetylases; preclinical studies.

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Figures

FIGURE 1
FIGURE 1
Hallmarks of cancer cell biology in which histone deacetylases (HDACs) are involved. Figure created with BioRender.com.
FIGURE 2
FIGURE 2
Effects of combined histone deacetylases inhibitors (pan- or selective HDACis) with different antitumor therapies on tumor cells. The diverse combinations with HDACis showed synergistic antitumor effects leading to a wide spectrum of biologic effects such as DNA damage, apoptosis induction, inhibition of proliferation and cellular stress. Figure created with BioRender.com.
See this image and copyright information in PMC

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