Epigenetic Therapies in Solid Tumours: From Preclinical Models to Clinical Trial Results

摘要: All types of cancer show widespread aberrant epigenetic changes, leading to changes in expression genes involved all the classic hallmarks cancer, as well how tumours will respond chemotherapy. These can be, at least temporarily, reversed using small molecule inhibitors maintenance state. Demethylating agents and histone deacetylase have shown activity against certain haematological malignancies; however, their solid remains more uncertain. For successful treatment with therapies, major challenges remain delivery therapy, a pharmacodynamic response achievement therapeutic index. In addition, development robust predictive biomarkers linked an understanding underlying biology be key improved therapy approaches. Defining profile individual subtypes may allow targeted those groups patients who are most likely benefit from this treatment. Furthermore, targeting drug-resistant or tumour-sustaining subpopulations tumour cells therapies vital, especially given role mechanisms stem cell Finally, overview published clinical trials drugs (alone combination other epi-drugs, differentiation-inducing agents, tyrosine kinase chemotherapy) is for different entities. results clearly demonstrate that approach has successfully entered arena. Examples include encouraging hypomethylating carboplatin platinum-refractory ovarian studies non-small lung cancer.