Wednesday 24 January 2018

PARP inhibitors for PTEN-mutant cancer cells

Most GBM tumors (IDH1 wild-type) have a loss of one copy of chromosome 10.  Additionally, about 30% will also have a deactivating mutation in the remaining copy of PTEN, leaving no functional PTEN in these tumors.

In these tumors, PARP inhibitors may be an effective therapeutic option, based on a study showing therapeutic effects of olaparib in PTEN-negative HCT116 colon cancer xenografts, while HCT116 xenografts with restored PTEN didn't respond to olaparib.

These results are not necessarily generally applicable, as the HCT116 line is also known to have mismatch repair defect (loss of MLH1), so there may have been some interaction between loss of both mismatch repair and PTEN that sensitized cells to olaparib.

Study title:
Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors
Full study available here

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