The Role of Thymidylate Synthase in Pemetrexed-Resistant Malignant Pleural Mesothelioma Cells
1058
effective drug even in pemetrexed-resistant cells. How-
ever, the mechanism of ECyd involves inhibition of RNA
biosynthesis, and ECyd has been considered a superior
antitumor nucleoside whose clinical trials are in progress
as TAS-106 in USA [20,21]. ECyd and pemetrexed be-
long to the same category as anti-metabolic drugs. How-
ever, their metabolic and activated pathways differ through
the pyrimidine and folate metabolic pathways, respec-
tively, bestowing ECyd with excellent antitumor activity
against many solid tumors [22-28]. Even in H/peme-
trexed cells, ECyd showed the same antitumor effect as
in MSTO-211H cells. Therefore, in the clinical treatment
of malignant pleural mesothelioma patients, ECyd may
be extremely useful as a promising second line drug. The
TYMS gene may be considered as a useful biomarker for
predicting pemetrexed chemosensitivity in malignant pleu-
ral mesothelioma patients.
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