# HDAC inhibitors as anticancer drugs: chemical diversity, clinical trials, challenges and perspectives

## TL;DR

This paper reviews HDAC inhibitors as anticancer drugs, comparing their chemical structures and clinical trial outcomes to guide future cancer therapies.

## Contribution

The study systematically analyzes the clinical performance and structural diversity of HDAC inhibitors in combination with other drugs.

## Key findings

- HDAC inhibitors are more effective when combined with drugs like doxorubicin, especially against solid tumors.
- They show significant results against lymphoma and leukemia as single agents.
- Combination therapies with HDAC inhibitors also work well for lymphomas and leukemias.

## Abstract

In an attempt to collect clinical data about HDAC inhibitors as very significant anticancer drugs we aimed to compare data and reveal the impact of the structural features, concluding the points of interest that are likely to help further development of better cancer therapy. We presented results of different clinical phases of HDAC inhibitors classified as hydroxamic acid derivatives, cyclic peptides, benzamides, and short chain aliphatic acids in a coherent and cohesive manner. It was found that HDAC inhibitors are preferentially combined with other antitumor drugs, mainly anti PD-1 and doxorubicin. In contrast, drugs such as docetaxel exaggerate the toxicity of HDAC inhibitors. Furthermore, data from clinical trials showed that the efficacy of HDAC inhibitors as single agents was limited against solid tumors. But they were significant against many solid tumors when combined with other anticancer agents. For example, combination of vorinostat and doxorubicin showed good results in solid tumors, especially prostate cancer, breast cancer, and melanoma. On the contrary, single agents of HDAC inhibitors revealed considerable clinical outcomes against different types of lymphoma and leukemia that warrant further investigation. Meanwhile, combinations of HDAC inhibitors and other drugs were also effective against lymphomas and leukemias.

In an attempt to collect clinical data about HDAC inhibitors as very significant anticancer drugs, we aimed to compare data and reveal the impact of the structural features to help – develop better cancer therapy.