Iniparib Phase III study in metastatic triple-negative breast cancer does not meet primary goal

Sanofi-aventis and its subsidiary, BiPar Sciences, today announced that a randomized Phase III trial evaluating iniparib (BSI-201) in patients with metastatic triple-negative breast cancer (mTNBC) did not meet the pre-specified criteria for significance for co-primary endpoints of overall survival and progression-free survival

Since superoxide is generally removed from the cell with the help of a detoxifying enzyme called manganese superoxide dismutase (MnSOD), Gius hypothesized that the Sirt3 deficiency may abnormally regulate MnSOD.

In the current study, the researchers show that Sirt3 knockout mice have decreased MnSOD activity despite having normal levels of the protein.

Gius and colleagues determined that the MnSOD in Sirt3 knockout mice was abnormally modified (with a chemical "acetyl" group) at a specific amino acid (lysine 122).

This aberrant modification of MnSOD reduced the enzyme’s ability to detoxify superoxide and appeared to explain the increase in ROS in Sirt3 knockout mouse tumors.

"These results suggest that aberrant regulation of MnSOD plays a role in receptor positive breast cancer," said Gius.

Gius and colleagues also developed an antibody that can assess the acetylation status of MnSOD, which he says can potentially be used "to screen breast tissue samples to determine what women are at risk for (receptor positive) cancer or for recurrence because of this dysregulation of MnSOD."

Additionally, agents that target the acetylation of this amino acid on MnSOD may be useful as chemopreventive therapies in women at risk of these cancers and of recurrence, he noted.

Source: Vanderbilt University Medical Center

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