Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Feb 1;329(1):1-8.
doi: 10.1016/j.canlet.2012.09.018. Epub 2012 Sep 29.

Combination Therapy: Histone Deacetylase Inhibitors and Platinum-Based Chemotherapeutics for Cancer

Affiliations
Free PMC article
Review

Combination Therapy: Histone Deacetylase Inhibitors and Platinum-Based Chemotherapeutics for Cancer

Himashinie V K Diyabalanage et al. Cancer Lett. .
Free PMC article

Abstract

One of the most promising strategies to increase the efficacy of standard chemotherapy drugs is by combining them with low doses of histone deacetylases inhibitors (HDACis). Regarded as chemosensitizers, the addition of well-tolerated doses of HDACis to platinum-based chemotherapeutics has been proven in vitro and in vivo in recent studies for many cancer types and stages. In this review, we discuss the most commonly used combinations of histone deacetylase inhibitors and platinum based drugs in the context of their possible mechanisms, efficiency, efficacy, and related drawbacks in preclinical and clinical studies.

Figures

Fig. 1
Fig. 1
Proposed mechanisms for synergistic effect of HDACi and cisplatin combined therapy HDACi induces hyperacetylation of histones, relaxing chromatin and rendering it more accessible for cisplatin. Treatment with low doses of HDACi sensitizes cells to further damage by cisplatin by initiating a pro-apoptotic state defined by increased caspase activity and decreased anti-apoptotic proteins. Glutathione, a major inactivator of cisplatin, is synthesized in lower quantities in HDACi-treated cells.
Fig. 2
Fig. 2
Bifunctional molecules with dual capability of HDAC inhibition and Platinum-DNA binding. a) cis-[Pt(NH3)2(malSAHA–2H)], b) trans-[Pt(VPA–1H)2(NH3)(py)]

Similar articles

See all similar articles

Cited by 22 articles

See all "Cited by" articles

MeSH terms

Feedback