'Epigenetic' therapy shows promise for hard-to-treat lung cancer

In collaboration with the Press Association

A new 'epigenetic' therapy appears to be able to prolong the life of patients with late-stage non-small cell lung cancer (NSCLC), according to the results of a small clinical trial published in the journal Cancer Discovery.

Forty-five patients with late-stage NSCLC who received a combination two-drug therapy survived around two months longer than would normally be expected.

Rather than killing dividing cells, like conventional chemotherapy, epigenetic therapies are devised to switch certain genes back on.

In healthy cells, some genes act to prevent cancer by stopping cells form dividing when they shouldn't. But tumour cells devise ways to silence these genes by binding and gagging them so that the cell is no longer able to use them - so-called 'epigenetic silencing'. So researchers have been developing epigenetic drugs that can reverse this, removing these molecular shackles to reinstate the anti-cancer activity of these genes.

The researchers from the Johns Hopkins Kimmel Cancer Center tested a combination epigenetic therapy of azacitidine and entinostat on patients with recurrent metastatic NSCLC. All the patients had already been treated with standard therapies, but their disease has subsequently progressed.

The trial had an 'open label' design, in which all patients received the treatment and there was no control group receiving placebo.

Patients survived on average for 6.4 months with treatment, compared with a typical survival rate of around four months for this patient population.

Following the epigenetic therapy, four of the 19 patients also had unexpectedly strong responses to further treatment with standard chemotherapies.

According to study author Dr Stephen Baylin, "This raises the possibility that the epigenetic treatment is having a delayed effect, or is even sensitizing patients' tumours in a way that makes them more vulnerable to subsequent therapies."

"This study appears to show the first durable successes in solid tumours with epigenetic therapy."

The preliminary findings were described as encouraging by Professor Tony Kouzarides, deputy director of the Wellcome Trust/Cancer Research UK Gurdon Institute at the University of Cambridge.

He said: "This is an encouraging step forward, even though it is an early-stage trial in a small number of people. More work is needed before such a treatment could be made more widely available, but this is a very good news for epigenetic therapy, which is still in its infancy.

"The research shows the potential for epigenetic drugs in the treatment of solid tumours, and provides a rationale for testing more such treatments in combination therapy. It's an exciting area of research, and one which my own group is actively working on for the treatment of leukaemia."

Copyright Press Association 2011

References

  • Juergens, R. et al. (2011). Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non-Small Cell Lung Cancer. Cancer Discovery DOI: 10.1158/2159-8290.CD-11-0214