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Mirna Therapeutics and Horizon Discovery Uncover Important Tumor Suppressor Pathway

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News

Mirna Therapeutics and Horizon Discovery Uncover Important Tumor Suppressor Pathway

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Mirna Therapeutics, Inc. and Horizon Discovery Ltd. announced today the publication of new data providing further confirmation that microRNA-34 (miR-34), and the tumor suppressor pathways it controls, is an important potential target for a wide variety of cancers. The data are published in Molecular Therapy, the official journal of the American Society of Gene and Cell Therapy, and reveals a novel mechanism through which miR-34 exerts its tumor suppressor function in cancers.

Mirna is currently conducting a Phase I study of MRX34, a miR-34-based therapy and the first microRNA mimic to advance into a human clinical trial. The Phase I study focuses on patients with unresectable primary liver cancer or metastatic cancer with liver involvement.
The data published in the paper entitled: “TP53-independent function of miR-34a via HDAC1 and p21CIP1/WAF1” demonstrate that the tumor suppressive activity of miR-34 is the same in p53-positive and p53-negative cancer cells. The study further revealed the existence of a p53-independent pathway by which miR-34 induces the expression of p21, a potent tumor suppressor inhibiting uncontrolled cellular proliferation. The endogenous level of p21 was shown to be critical for maximal miR-34 activity.

“The identification of an alternative pathway to induce p21 expression is a significant discovery in cancer biology with wide ranging implications for therapeutic interventions to overcome inhibition of programmed cell death,” says Andreas Bader, Ph.D., Mirna’s Director of Analytical and External Research, and senior author of the publication. “Particularly exciting is the observation that miR-34 functions similarly to p53, suggesting that miR-34 replacement therapy might represent an attractive alternative to p53-targeted therapy.”

Chris Torrance, Ph.D., Chief Scientific Officer, Horizon Discovery, said: “We were delighted to collaborate with Mirna on this project, which involved supply of X-MAN isogenic cell lines to examine the effects of specific mutations to the TP53 gene. The results are very exciting, and we look forward to seeing the outcome of Mirna’s Phase I study.”

The research was supported by a grant from the National Institutes of Health, and a commercialization grant from the Cancer Prevention and Research Institute of Texas (CPRIT).

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