Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: A Hoosier Oncology Group phase II trial

Moore, Annette M.; Einhorn, Lawrence H.; Estes, D.; Govindan, Ramaswamy; Axelson, John A.; Vinson, Jacob; Breen, T.; Yu, Menggang; Hanna, Nasser H.

doi:10.1016/j.lungcan.2005.12.002

Cited by 88 publications

(58 citation statements)

References 26 publications

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“…Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been widely used in non-small cell lung cancer (NSCLC) (9-13), but have failed to treat relapsed SCLC (14). The incidence of EGFR mutation in NSCLC is higher in China than in the United States of America and European countries (15,16).…”

Section: Introductionmentioning

confidence: 99%

“…C-kit expression is high in SCLC, and strong staining correlates to to worse survival prognosis. The incidence of EGFR exons 19 and 21 mutation in SCLC is extremely low in China and Japan (22)(23)(24), and gefitinib failed to demonstrate benefit in relapsed SCLC patients (14). Given the limited therapeutic options and unfavorable prognosis of SCLC, increased interest and studies are required to develop targeted therapies to improve survival.…”

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confidence: 99%

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Expression and mutation of the c-kit gene and correlation with prognosis of small cell lung cancer

Cheng

et al. 2012

Oncology Letters

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Abstract. Small cell lung cancer (SCLC) is a highly aggressive and lethal type of cancer in humans. SCLC is sensitive to chemotherapy and radiotherapy, but long-term survival is low and the majority of patients eventually develop progressive disease. With the success of imatinib mesylate in the treatment of gastrointestinal stromal tumors expressing c-kit, its use in SCLC serves as a novel molecular therapeutic approach. The activity of imatinib mesylate is correlated with the mutation of c-kit gene exons 9 and 11 in gastrointestinal stromal tumors. The incidence of epidermal growth factor receptor mutation in non-small cell lung cancer is higher in China than in the United States of America and European countries. There may be also differences in the incidence of c-kit mutation between China and European countries. At present, no study examining imatinib mesylate treatment for SCLC in China is available. To investigate the expression and mutation of c-kit and the correlation with prognosis of SCLC in China, immunohistochemistry was used to detect the expression of c-kit, and a pyrosequencing assay was used to detect mutations in c-kit exons 9 and 11 of 36 SCLC patients who received surgical treatment at the Zhejiang Cancer Hospital, Hangzhou, China, between 1998 and 2010. All 36 patients were followed up to analyze the correlation between prognosis and expression and mutation of c-kit. The incidence of c-kit-positive expression was 83.3%, including 25.0% weak staining, 22.2% moderate staining and 36.1% strong staining. The overall survival of patients with c-kit strong staining was shorter compared to patients with c-kit not strong staining. No mutation in c-kit exons 9 and 11 was detected. In conclusion, the findings showed that the expression of c-kit is high, and strong staining is a prognostic factor for worse survival.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Expression and mutation of the c-kit gene and correlation with prognosis of small cell lung cancer

Cheng

et al. 2012

Oncology Letters

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“…Two patients had stable disease (SD) and 17 had progressive disease (PD). This study failed to demonstrate a benefit from the use of gefitinib in SCLC patients (18). EGFR mutation is important for gefitinib and erlotinib therapy in advanced NSCLC, especially in first-line therapy, and it may also be significant in SCLC.…”

Section: Growth Factor Receptor Inhibitorsmentioning

confidence: 67%

Targeted therapies in small cell lung cancer (Review)

Wang

Mao

2012

Oncol Lett

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Abstract. Lung cancer is the leading cause of cancer-related mortality. Small cell lung cancer (SCLC) accounted for 12.95% of all lung cancer histological types in 2002. Despite trends toward modest improvement in survival, the outcome remains extremely poor. Chemotherapy is the cornerstone of treatment in SCLC. More than two-thirds of patients who succumb to lung cancer in the United States are over 65 years old. Elderly patients tolerate chemotherapy poorly and need novel therapeutic agents. Targeted drugs have less toxicity than chemotherapy drugs, but no targeted agents have been approved for use in the treatment of SCLC patients to date. Certain new targeted agents, including gefitinib, bevacizumab and Bcl-2 inhibitors, offer a promise of improved outcomes, however negative results are more commonly reported than positive. This review focuses on targeted therapies in SCLC.

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“…Targeting cell surface RTKs is an attractive strategy for cancer treatment. In fact, several clinical trials targeting RTKs such as c-Kit and EGFR by TKIs have been conducted in SCLC but eventuated in disappointing results (35,36). We here tested the antitumor activity of targeting HER2 by lapatinib as monotherapy at clinically achievable concentration in vitro.…”

Section: Discussionmentioning

confidence: 99%

HER2 As Therapeutic Target for Overcoming ATP-Binding Cassette Transporter–Mediated Chemoresistance in Small Cell Lung Cancer

Minami

Kijima

Otani

et al. 2012

Molecular Cancer Therapeutics

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Small cell lung cancer (SCLC) easily acquires multidrug resistance after successful initial therapy. Overexpression of ATP-binding cassette (ABC) transporters is important for the multidrug resistance. Among them, ABCB1 and ABCG2 are known to be upregulated in chemoresistant SCLC cells. We found that human epidermal growth factor receptor 2 (HER2) expressions are also upregulated in chemoresistant SBC-3/ETP, SBC-3/SN-38, and SBC-3/CDDP cells, compared with chemosensitive SBC-3 cells. Lapatinib, a tyrosine kinase inhibitor of HER2, could not suppress proliferation of these HER2-positive SCLC cells alone but successfully restored chemosensitivity to etoposide and SN-38 with a clinically applicable concentration. The reversal effect of lapatinib was thought to be caused by inhibition of drug efflux pump functions of ABC transporters, although lapatinib itself has been reported to be a substrate for them. Moreover, knocking down of HER2 by an short interfering RNA weakened the effect of lapatinib on ABCB1, indicating the involvement of HER2 in the inhibitory mechanisms. Notably, we showed that caveolin-1 and Src play key roles in modulating ABCB1 function via HER2 inactivation. In SBC-3/ETP cells, dephosphorylation of HER2 by lapatinib activates Src and successively leads to increased caveolin-1 phosphorylation. Through this process, caveolin-1 dissociates from HER2 and strengthens association with ABCB1, and finally impairs the pump functions. Furthermore, we showed that treatment by lapatinib in combination with etoposide or irinotecan significantly suppresses the growth of subcutaneous SBC-3/ETP and SBC-3/SN-38 tumors in mice, respectively. Collectively, these results indicate that combination therapy with lapatinib and cytotoxic agents could conquer ABC transportermediated chemoresistance especially in HER2-positive SCLC. Mol Cancer Ther; 11(4); 830-41. Ó2012 AACR.

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Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: A Hoosier Oncology Group phase II trial

Cited by 88 publications

References 26 publications

Expression and mutation of the c-kit gene and correlation with prognosis of small cell lung cancer

Expression and mutation of the c-kit gene and correlation with prognosis of small cell lung cancer

Targeted therapies in small cell lung cancer (Review)

HER2 As Therapeutic Target for Overcoming ATP-Binding Cassette Transporter–Mediated Chemoresistance in Small Cell Lung Cancer

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