Histone Deacetylase Inhibitors and Phenotypical Transformation of Cancer Cells

Area of Science:

• Epigenetics and Cancer Biology
• Pharmacology of Anticancer Agents

Background:

• Histone deacetylase inhibitors (HDIs) are epigenetic drugs with therapeutic potential in malignancies.
• HDIs are used clinically and in trials, showing efficacy in inhibiting cancer cell growth.
• Conflicting reports on HDI pro-invasive and anti-invasive activities necessitate further investigation.

Purpose of the Study:

• To review recent findings on the effects of HDIs on epithelial-mesenchymal transition (EMT) in human cancers.
• To analyze HDI impact on key EMT markers, activators, and cancer cell invasive properties.
• To discuss HDI applications in monotherapy and combination treatments concerning EMT modulation.

Main Methods:

• Literature review of recent studies on HDIs and EMT in human cancers.
• Summary of HDI effects on epithelial markers (E-cadherin, β-catenin) and mesenchymal markers (N-cadherin, vimentin).
• Analysis of HDI influence on EMT activators (TWIST, SNAIL, SLUG, SMAD, ZEB), cell morphology, migration, and invasion.

Main Results:

• HDIs modulate epithelial and mesenchymal markers, affecting cancer cell plasticity.
• Impact of HDIs on EMT activators like TWIST, SNAIL, SLUG, SMAD, and ZEB is documented.
• HDIs influence cancer cell morphology, migration, and invasion potential, with varied effects reported.

Conclusions:

• HDIs exhibit complex effects on EMT, influencing cancer cell invasion and progression.
• Understanding HDI-mediated EMT changes is crucial for optimizing cancer therapy.
• HDIs hold potential as monotherapy or in combination regimens, contingent on their EMT-modulating effects.