The "Guardian of the Genome"-An Old Key to Unlock the ERCC1 Issue
CLINICAL CANCER RESEARCH
Authors: Friboulet, Luc; Soria, Jean-Charles; Olaussen, Ken Andre
Abstract
Excision Repair Cross-Complementation Group 1 (ERCC1) participates in the repair of DNA intrastrand adducts (ISA) and interstrand cross-links, but its role as a predictive biomarker has never been fully validated. It has now been revealed that p53 mutation status should be considered concomitantly with ERCC1 to predict cisplatin efficacy.
The relationship between the expression of thymidylate synthase, dihydropyrimidine dehydrogenase, orotate phosphoribosyltransferase, excision repair cross-complementation group 1 and class III beta-tubulin, and the therapeutic effect of S-1 or carboplatin plus paclitaxel in non-small-cell lung cancer
MOLECULAR AND CLINICAL ONCOLOGY
Authors: Okuda, Katsuhiro; Tatematsu, Tsutomu; Yano, Motoki; Nakamae, Katsumi; Yamada, Takeshi; Kasugai, Toshio; Nishida, Tsutomu; Sano, Masaaki; Moriyama, Satoru; Haneda, Hiroshi; Kawano, Osamu; Sakane, Tadashi; Oda, Risa; Watanabe, Takuya; Nakanishi, Ryoichi
Abstract
Previous studies have reported that the expressions of specific proteins may predict the efficacy of chemotherapy agents for non-small cell lung cancer (NSCLC) patients. The present study evaluated the expression of proteins hypothesized to be associated with the effect of chemotherapeutic agents in 38 NSCLC patients with pathological stage II and IIIA. The subjects received carboplatin plus paclitaxel (CP) or S-1 as adjuvant chemotherapy following complete resection. The protein expressions evaluated were those of thymidylatce synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phsphoribosyltransferase (OPRT), which were suspected to be associated with the effect of S-1 agents, excision repair cross-complementation group 1 (ERCC1), which was suspected to be associated with the effect of platinum-based agents, and class III beta-tubulin (TUBB3), which was suspected to be associated with the effect of taxane-based agents. The positive rate of TS was 55.3% (n=21/38), DPD was 57.9% (n=2238), OPRT was 42.1% (n=16/38), ERCC1 was 47.4% (n=18/38) and TUBB3 was 44.7% (n=17138). Among the patients who received S-1 adjuvant chemotherapy, TS-negative cases demonstrated a significantly better disease-free survival than positive cases. Thus, TS protein expression may have been a factor that predicted the effect of S-1 agent as adjuvant chemotherapy.