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Combo of novel HDAC, mTOR inhibitors induced pancreatic cancer cell death
AACR 100th Annual Meeting
The combination of an mTOR inhibitor with a histone deacetylase inhibitor, both of which play key roles in the biological formation of tumors, may interfere with the survival and proliferation pathways of pancreatic cancer cells, according to a late-breaking abstract presented at the AACR 100th Annual Meeting.
“Our data suggest that combining an mTOR inhibitor with a HDAC inhibitor such as LBH589 may have potential to be used as a new therapeutic intervention against this deadly disease,” Mamta Gupta, PhD, a research associate in the Mayo Clinic Cancer Center in Rochester, Minn., said at the meeting.
Gupta and colleagues tested the mTOR inhibitor rapamycin and the HDAC inhibitor LBH589 (panobinostat) both alone and in combination to measure cell survival on pancreatic cancer cell lines in vitro.
Treatment with various doses of rapamycin alone resulted in a less than 10% reduction in overall cell survival; LBH589 alone killed about 50% of cultured cells.
However, combined treatment with rapamycin and LBH589 resulted in cell death between 60% and 70%, depending upon cell lines.
The results of the study are significant because the three cell lines studied — MIAPaCa-2, Pnac-1, BxPc-3 — are all resistant to chemotherapy and because both drugs are already available for treatment, according to Gupta. – by Leah Lawrence
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