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alignant pleural mesothelioma is an aggressive tumor, closely related to asbestos exposure. It remains a significant worldwide health problem because of its poor prognosis and increasing incidence.
Most of the patients have advanced disease at diagnosis and are not eligible for surgical treatment. Thus, therapy is generally combined chemotherapy to improve symptoms and modestly increase survival.
Currently the combination of Cisplatin and Pemetrexed is the widely used regimen for the systemic treatment of the disease.
Cisplatin works by binding to the DNA forming adducts that lead to intra- or inter-strand cross-links. The formation of these DNA cross-links inhibits cell replication and drives it toward apoptosis. The cells have intrinsic ability to identify and repair this DNA damage by the Nucleotide excision repair which unwound DNA helix, ERCC1 then form a complex with (XPF) which excise the damaged DNA area. DNA polymerase then resynthesizes the absent part of DNA when NER-nucleotide excision repair is complete, the DNA is repaired and resumes its normal helical shape.
In case of ERCC1 deficiency, the DNA damage is not repaired, and the altered DNA is unable to replicate, or perform its function, leading to cell damage.
Expression of ERCC1 has been studied as a predictive marker for Cisplatin resistance in different tumors including MPM. Four previously published studies showed a significant correlation between Negative expression of ERCC1 and good response to Cisplatin and also with longer PFS.
Our study showed that ERCC1 was expressed in 33.9% of the patients.
ERCC1 positivity was significantly associated with poor response to treatment, shorter PFS & OS.