Despite their potential, HDAC inhibitors face several challenges:
1. Toxicity and Side Effects: HDACis can affect normal cells, leading to side effects such as fatigue, gastrointestinal issues, and hematological toxicity. 2. Resistance: Cancer cells can develop resistance to HDACis through various mechanisms, including alterations in drug uptake and efflux, and compensatory activation of other pathways. 3. Target Specificity: HDACs have broad roles in cellular physiology, and targeting them specifically in cancer cells while sparing normal cells remains a challenge.
