A team of scientists from Columbia University Medical Center has formulated a new, synergistic method of potential treatment for patients with mantle cell lymphoma.
Mantle cell lymphoma (MCL) is an aggressive and currently incurable cancer of the white blood cells, with an average survival rate of only a few years. The goal of this new study is to develop a better treatment that increases the length and quality of life for patients suffering with MCL.
Researchers from Columbia University Medical Center in New York City have recently published the research paper in Oncotarget, an open-access scientific journal, detailing their study to develop this new potential treatment method for patients with MCL.
New Synergistic Treatment Combination for MCL
Histone deacetylation (HDAC) inhibitors are commonly used as anti-cancer drugs and considered highly effective in the treatment of select lymphomas. The team used the HDAC inhibitor romidepsin to induce cell cycle arrest and activate p21 gene expression in cells with MCL.
While romidepsin increases the expression of p21, researchers found that inducing p21 also reduces the efficacy of this HDAC inhibitor. To combat this issue, the team proposed sequentially administering KU60019, an ATM inhibitor, to nullify the HDAC induction of p21 expression and encourage a shift to the apoptotic phase (cell death) in lymphoma cells. KU60019 is a chemical compound that selectively inhibits the ATM gene to override the protective effect of romidepsin observed with p21 induction and thus, increases its cytotoxic effect.
The team conducted a statistical analysis that confirms this method of targeted sequential therapy is effective in their in vitro (outside living organisms) studies and also suggests that it offers less toxicity for the normal lymphocytes (healthy white blood cells).
The Mouse Model
To evaluate this new method of treatment in vivo, or within a living organism, the team conducted an experiment to test 32 mice with MCL, divided into four groups of eight. Group one was injected only with saline (the control group); group two was injected with romidepsin; group three was injected with KU60019; and group four was sequentially injected with a combination of both romidepsin and KU60019. The mice were treated over the course of a three week cycle.
In the combination group, romidepsin was administered each week on days one, eight, and 15, and KU60019 was administered on days one through five of each week. The mice were monitored for 40 days post-enrollment.
Survival was significantly improved in the mouse group that was treated with the combination of romidepsin and KU60019 compared to mice treated with a single compound.
This study revealed the combination method the team used with romidepsin and KU60019 had superior results in mice with MCL compared to both of the compounds when administered individually. Tumor cells decreased substantially in the combination group, proving it is a highly synergistic method of sequential treatment.
The researchers note that for a clearer understanding of the molecular pharmacological features of this combination, these approaches must be translated to clinical trials in order to establish therapeutic merit in the clinic.
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Click here to read the full scientific paper, published in Oncotarget.