Novel Therapeutic Approaches for Small Cell Lung Cancer: The Future has Arrived

Pietanza, M. Catherine; Rudin, Charles M.

doi:10.1016/j.currproblcancer.2012.03.005

Cited by 6 publications

(3 citation statements)

References 98 publications

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“…Currently, no effective treatments are available to cure SCLC or other NE lung tumors. Conventionally, SCLC is initially treated by combination chemotherapy using cisplatin or carboplatin plus etoposide with an option to include radiation therapy, which results in overall high response rates (60–80%) ( 4 ). However, tumors relapse within months after the initial therapy and topotecan is the only approved agent for recurrent or progressive SCLC ( 31 , 32 ).…”

Section: Discussionmentioning

confidence: 99%

“…Lung cancer is currently the leading cause of cancer death in men and women, causing more deaths than colon, breast and prostate cancer combined ( 1 ). Lung cancers are mainly classified into small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC), but lung cancers are also sub-classified depending upon different characteristics and origins of progenitor cells ( 2 – 4 ). For example, neuroendocrine (NE) phenotypes characterize a spectrum of tumors, including low-grade typical and intermediate-grade atypical carcinoid, high-grade large-cell NE carcinoma and SCLC ( 5 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

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Autophagy sensitivity of neuroendocrine lung tumor cells

Hong

Kim

Starenki

et al. 2013

International Journal of Oncology

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Neuroendocrine (NE) phenotypes characterize a spectrum of lung tumors, including low-grade typical and intermediate-grade atypical carcinoid, high-grade large-cell NE carcinoma and small cell lung carcinoma. Currently, no effective treatments are available to cure NE lung tumors, demanding identification of biological features specific to these tumors. Here, we report that autophagy has an important role for NE lung tumor cell proliferation and survival. We found that the expression levels of the autophagy marker LC3 are relatively high in a panel of lung tumor cell lines expressing high levels of neuron-specific enolase (NSE), a key NE marker in lung tumors. In response to bafilomycin A1 and chloroquine, NE lung tumor cells exhibited cytotoxicity whereas non-NE lung tumor cells exhibited cytostasis, indicating a distinct role of autophagy for NE lung tumor cell survival. Intriguingly, in certain NE lung tumor cell lines, the levels of processed LC3 (LC3-II) were inversely correlated with AKT activity. When AKT activity was inhibited using AKTi or MK2206, the levels of LC3-II and SQSTM1/p62 were increased. In contrast, torin 1, rapamycin or mTOR knockdown increased p62 levels, suggesting that these two pathways have opposing effects on autophagy in certain NE lung tumors. Moreover, inhibition of one pathway resulted in reduced activity of the other, suggesting that these two pathways crosstalk in the tumors. These results suggest that NE lung tumor cells share a common feature of autophagy and are more sensitive to autophagy inhibition than non-NE lung tumor cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Autophagy sensitivity of neuroendocrine lung tumor cells

Hong

Kim

Starenki

et al. 2013

International Journal of Oncology

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show abstract

“…Therefore, p53 has been suggested as a potential antigenic target to use with immunotherapeutic strategies (Freeman-Keller, Goldman, Gray, 2015). There are also reports on immunotherapeutic approaches for SCLC using vaccines for specific antigens, such as gangliosides (Pietanza, Rudin, 2012;Hall, Gray, Chiappori, 2013).…”

Section: Immunotherapymentioning

confidence: 99%