A team of American scientists have shown that an epigenetic therapy might hold promise for combatting drug resistance in cancer.
Cancer cells are masters of drug evasion and adept at using alternative pathways to give them an edge during treatment, complicating many therapeutic approaches. Overcoming drug resistance in cancer cells, would save millions of lives and drastically cut treatment costs.
Epigenetic reprogramming fueled by DNA methylation changes, chromatin reconfiguration, histone modification, and/or noncoding RNAs, is very common in most human cancers. Important tumor suppressors are often epigenetically silenced either via DNA methylation or histone deacetylation and thus are unable to perform their tumor suppressive functions. As a result, reprogramming the reprogramming might help cancer treatment in resistance scenarios.
Hasanali and colleagues set out to determine whether combinatorial epigenetic therapy can provide an alternative cure for patients with T cell prolymphocytic leukemia (T-PLL). To achieve their aim, they threw the “kitchen sink” combination of demethylating agents, histone deacetylase (HDAC) inhibitors, and the immunotherapeutic agent, Brentuximab vedotin, to treat eight patients with T-PLL resistant to the conventional treatment, alemtuzumab.
Here is what the team learned:
- Introducing epigenetic agents such as cladribine induced the expression of tumor necrosis factor receptor superfamily member 8, TNFRSF8 (CD30), a well studied and frequently targeted cancer marker
- Adding epigenetic agents to alemtuzumab treatment overcomes resistance to alemtuzumab in T-PLL patients.
- Remarkably, seven out of the eight patients that received this treatment achieved complete remission, and the eighth patient achieved partial remission.
These results add to previous data that suggest a promising future for combinatorial epigenetic therapy in cancer treatment.
Explore how to make cancer cells defenseless at Science Translational Medicine, June 2015.