Expression of breast cancer resistance protein is associated with a poor clinical outcome in patients with small-cell lung cancer

Kim, Young Hak; Ishii, Genichiro; Goto, Kōichi; Ota, Shuji; Kubota, Keiichi; Murata, Yukinori; Mishima, Michiaki; Saijo, Nagahiro; Nishiwaki, Yutaka; Ochiai, Atsushi

doi:10.1016/j.lungcan.2008.10.008

“…Expression of ABCG2 has been observed in the epithelial cells of the intestine, colon, liver canaliculi, renal tubules and placenta, where it eliminates anticancer drugs and ingested toxins (9). The association between overexpression of ABCG2, response to chemotherapy and prognosis has been ABCG2 expression in colorectal adenocarcinomas may predict resistance to irinotecan reported for leukemia (10) and various solid tumors, including breast cancer (11), oral squamous cell carcinoma (12), esophageal cancer (13) and lung cancer (14). Irinotecan and its active metabolite, SN-38, are included among the transport substrates of ABCG2 (15).…”

Section: Introductionmentioning

confidence: 99%

ABCG2 expression in colorectal adenocarcinomas may predict resistance to irinotecan

Tuy

¹

,

Shiomi

²

,

Mukaisho

³

et al. 2016

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Abstract. Irinotecan is a key drug for patients with advanced and recurrent colorectal carcinoma. However, the efficacy of irinotecan is not sufficient; partly, as there is no useful marker to predict chemosensitivity to the drug. The aim of the present study was to evaluate whether the expression levels of adenosine triphosphate-binding cassette sub-family G (WHITE) member 2 (Junior blood group) (ABCG2) in primary colorectal tumors predict chemoresistance to irinotecan. Using the resected primary tumor specimens of 189 patients with colorectal cancer, the association between the immunohistochemical expression of ABCG2 protein and the results of the collagen gel droplet embedded culture drug sensitivity test, performed to evaluate the chemosensitivity to SN-38 (an active metabolite of irinotecan), was investigated. Among the 189 patients, 17 received irinotecan-based chemotherapy, and their responses and progression-free survival (PFS) were analyzed. The tumors of patients with increased ABCG2 expression accounted for 60% of the tumors examined, and were significantly more resistant to SN-38, compared with patients with low ABCG2 expression (P<0.001). In a multivariate logistic regression analysis, increased expression of ABCG2 protein was an independent and significant predictor of resistance to SN-38, increasing the risk of resistance by 12-fold. Increased expression of ABCG2 and a low sensitivity to SN-38 was significantly associated with resistance to irinotecan-based chemotherapy (P=0.01 and 0.028, respectively). The median PFS of patients with increased expression of ABCG2 was significantly shorter, compared with patients with low expression levels of ABCG2 (104 vs. 242 days; P=0.047). The increased immunohistochemical expression of ABCG2 in primary tumors may be a useful predictive biomarker of resistance to irinotecan-based chemotherapy for patients with recurrent or metastatic colorectal cancer.

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“…Several studies have identified genes or proteins in lung cancer whose expression levels are associated with response to antitumor drugs. The breast cancer resistant protein (BCRP), is one of the ABC transporters reported to be associated with resistance to anticancer drugs like doxorubicin, irinotecan, mitoxantrone, and its expression was found to be associated with a poor clinical outcome in SCLC patients undergoing chemotherapy [Kim, 2009]. Chiappori et al reported that RRM1 and Topo2 alpha proteins expression are biomarkers of chemotherapeutic efficacy in SCLC [Chiappori, 2010] and, recently, Usuda et al demonstrated that the expression levels of Klotho protein was correlated with the prognosis following resection in SCLC patients [Usuda, 2011].…”

Section: Targeting the Complex Biology Of Sclcmentioning

confidence: 99%

Surgery in Small-Cell Lung Cancer: Past, Present and Future

Rapicetta¹,

Tenconi²,

Ricchetti³

et al. 2012

Lung Diseases - Selected State of the Art Reviews

0

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“…Several studies have identified genes or proteins in lung cancer whose expression levels are associated with response to antitumor drugs. The breast cancer resistant protein (BCRP), is one of the ABC transporters reported to be associated with resistance to anticancer drugs like doxorubicin, irinotecan, mitoxantrone, and its expression was found to be associated with a poor clinical outcome in SCLC patients undergoing chemotherapy [Kim, 2009]. Chiappori et al reported that RRM1 and Topo2 alpha proteins expression are biomarkers of chemotherapeutic efficacy in SCLC [Chiappori, 2010] and, recently, Usuda et al demonstrated that the expression levels of Klotho protein was correlated with the prognosis following resection in SCLC patients [Usuda, 2011].…”

Section: Targeting the Complex Biology Of Sclcmentioning

confidence: 99%