PARP inhibitor plus epigenetic inhibitor reduces cancer growth and survival

breast cancer

Poly(ADP-ribose) polymerase inhibitors (PARPis) are an exciting class of cancer drugs currently used in the clinic. To date, however, patients with acute myeloid leukemia--a cancer with a notoriously poor outcome after diagnosis--have failed to respond to them. Scientists have recently shown that combining PARPis with an epigenetic modifier significantly reduces cancer growth and survival of leukemia cells. 

Senior author Feyruz Rassool and her colleagues at the University of Maryland published their results in the journal Cancer Cell.

PARP1 is a protein that repairs single-strand breaks of DNA, and so a therapeutic strategy to target cancer cells is to inhibit this protein, leading to DNA damage and cell death. It fails to show any benefit in AML patients, however, and effective AML drug development therefore remains an unmet need.

FREE DAILY NEWSLETTER

Like this story? Subscribe to FierceBiotech!

Biopharma is a fast-growing world where big ideas come along every day. Our subscribers rely on FierceBiotech as their must-read source for the latest news, analysis and data in the world of biotech and pharma R&D. Sign up today to get biotech news and updates delivered to your inbox and read on the go.

Using both a cell line and a mouse model, Rassool and her group combined an investigational PARPis drug (called talazoparib) with a DNA methyltransferase inhibitor (DNMTi) and found a significant reduction in the growth and survival of these cancer cells. The addition of DNMTi is thought to boost the interaction of PARPis to further block DNA repair, leading to greater cell death in the AML cancers.

The research group believes the effect of combining the two drugs isn’t simply additive but rather synergistic, meaning there’s a direct interaction between the drugs, improving the response to both.

"Our preclinical data suggest that combining low doses of these inhibitors will enhance the clinical effects of both drugs as a potential treatment for patients with AML,” said Rassool in a statement.

She believes that despite a measly 10% long-term survival rate of patients with AML, this therapeutic approach may be the solution. It’s also thought that this combination may help other patients, such as those with lung, prostate and ovarian cancers.  

Suggested Articles

VISTA represents a novel checkpoint regulator that can be targeted by both agonists and antagonists to trigger opposing therapeutic T-cell effects.

An engineered vaccinia virus carrying two cytokines that stimulate anti-cancer responses prompted tumor regression in mouse models of three cancers.

In roundworm models of Parkinson's, probiotic Bacillus subtilis lowered the buildup of alpha-synuclein in the brain—a culprit in the disease.