DNA damage response plays a crucial role in response to platinum-based chemotherapy regimens, which are often used to treat malignant pleural mesothelioma (MPM).
Now, researchers have identified several key genes known to participate in DNA repair mechanisms that may serve as markers for predicting patients’ response to platinum-based therapies.
The study, “Screening of Pleural Mesotheliomas for DNA-damage Repair Players by Digital Gene Expression Analysis Can Enhance Clinical Management of Patients Receiving Platin-Based Chemotherapy,” published in the Journal of Cancer, may lead to enhanced clinical management and, thus, improved outcomes in MPM patients.
Currently, multimodality therapy consisting of chemotherapy, surgery, and radiotherapy uses platinum-based chemotherapy combined with Alimta (pemetrexed) as the treatment of choice. But this treatment is often associated with poor efficacy.
The reasons for the rather poor effectiveness of platinum-compound agents, such as Paraplatin (carboplatin) and Platinol (cisplatin), remain largely unknown, but since these agents work by inducing damages in the DNA of cancer cells, the ability of these cells to detect and repair such damages may be one of the characteristics that influence patients’ outcomes following platinum-based therapies.
To understand the impact of DNA damage response and repair key players on platinum-based therapy, researchers analyzed the expression of certain genes involved in these mechanisms in tumors from 24 MPM patients.
In this cohort, 12 patients had received Alimta/Platinol or Alimta/Platinol/Paraplatin as adjuvant therapy (given after surgery) and 12 had received Platinol followed by Alimta as neoadjuvant treatment (given before surgery).
Researchers analyzed a total of 366 genes, 30 of which were related to the cell’s ability to recognize and repair DNA damage. The team was able to identify several genes whose expression was associated with several aspects of MPM disease.
“In particular, CHEK1, XRCC2 and TP73 are strongly associated with tumor progression,” the researchers wrote, adding that these markers may be potentially used when staging the tumor.
“MLH1, CHEK1, ERCC1, and most promising, CDKN2A, are prognostic markers for OS [overall survival] in MPM,” they said. “Therefore, we suggest that these markers are at staging and upon diagnosis of MPM. TP73, CDKN2A, CHEK1, and ERCC1 seem to be also predictive markers in adjuvant treated MPMs.”
The researchers suggest that these markers should now be validated prospectively in MPM patients, so that they can eventually enter clinical practice and improve the management of these patients.