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L. Petersen
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-105 - PARP Inhibition Sensitises ATM Deficient NSCLC Cells to Cisplatin Treatment (ID 3037)
09:30 - 09:30 | Author(s): L. Petersen
- Abstract
Background:
We have previously demonstrated that non-small cell lung cancer (NSCLC) cells with low or undetectable ATM are sensitive to synthetic lethality with PARP inhibitor as a single agent. In contrast, lack of ATM alone does not seem to predict sensitivity of these cells to other agents such as cisplatin, a part of standard chemotherapy often used in NSCLC with limited efficacy. Because Cisplatin can induce some DNA damage that can activate ATM, we sought to determine whether PARP inhibition will improve cisplatin efficacy in NSCLC cells that are ATM deficient.
Methods:
A panel of NSCLC cell lines (NCI-H23, NCI-H460, NC1-H522, NCI-H1373) were assessed for ATM status by western blot in terms of a) ATM protein levels and b) ATM functionality by examining active phosphorylated ATM and downstream targets of ATM e.g. p53 and KRAB-associated protein 1 (KAP1) in irradiated cells. The biological effects of PARP-1 inhibition and cisplatin on viability of these cells were examined using the clonogenic survival assay.
Results:
Two NSCLC cell lines H23 and H1373 were found to be ATM deficient and they show increased sensitivity to the combination of cisplatin with PARP inhibition using olaparib, (Table 1). Figure 1
Conclusion:
Here, we show that PARP inhibitor sensitized ATM deficient NSCLC cells to cisplatin. These results suggest that a significant treatment response could be achieved in ATM deficient NSCLC cells with low dose cisplatin and PARP inhibition. We have evidence to suggest that ATM deficiency may be present in as much as 20 - 25% of NSCLC patients. This cohort may be able to benefit from modified therapy using lower dose chemotherapy, producing milder side effects and better quality of life.
