Molecular factors associated with pemetrexed sensitivity according to histological type in non-small cell lung cancer

Tsukihisa Yoshida, Tatsuro Okamoto, Tokujiro Yano, Kazuki Takada, Mikihiro Kohno, Kenichi Suda, Mitsuhiro Takenoyama, Yoshinao Oda, Yoshihiko Maehara

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3 Citations (Scopus)

Abstract

Background: This study was designed to investigate potential molecules that predict chemosensitivity to pemetrexed (Alimta®) in surgically resected non-small cell lung cancer (NSCLC). Materials and Methods: Chemosensitivity to ALM and other drugs was assessed by succinate dehydrogenase inhibition (SDI) test in 69 NSCLC samples (55 adenocarcinomas, and 14 squamous cell carcinomas). The mRNA expression levels of Alimta®-target enzymes [thymidylate synthase (TYMS); dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT)], Alimta®-metabolizing enzymes [γ-glutamyl hydrase (GGH) and folylpolyglutamate synthase] and an Alimta® transporter [reduce folate carrier (RFC)] were measured and examined for potential correlations to chemosensitivity. Results: The squamous cell carcinoma samples showed higher TYMS expression and lower RFC expression than did the adenocarcinoma samples. In the adenocarcinoma sample analyses, GGH expression was inversely correlated to sensitivity. Conclusion: The histology-dependent differences in chemosensitivity to Alimta® may be attributed to the histology-dependent differences in TYMS and RFC expression. In adenocarcinomas, GGH potentially represents a marker for chemosensitivity to Alimta®.

Original languageEnglish
Pages (from-to)6319-6326
Number of pages8
JournalAnticancer research
Volume36
Issue number12
DOIs
Publication statusPublished - Dec 2016

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Yoshida, T., Okamoto, T., Yano, T., Takada, K., Kohno, M., Suda, K., Takenoyama, M., Oda, Y., & Maehara, Y. (2016). Molecular factors associated with pemetrexed sensitivity according to histological type in non-small cell lung cancer. Anticancer research, 36(12), 6319-6326. https://doi.org/10.21873/anticanres.11228