Gene therapy for lung cancer

Toloza, Eric M.; Morse, Michael A.; Lyerly, H. Kim

doi:10.1002/jcb.20851

Cited by 26 publications

(10 citation statements)

References 94 publications

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“…Lung cancer develops through the acquisition of alterations in oncogenes, such as EGFR (10–40% of ADC) and KRAS (10–30% of ADC), and tumor suppressor genes, such as TP53 (~90% of SCLC; 50% of NSCLC), RB1 (~90% of SCLC; ~20% of NSCLC), CDKN2A/p16 (~50% of NSCLC), and LKB1/STK11 (20–30% of NSCLC) (Minna et al, 2002; Herbst et al, 2008). The EGFR, KRAS , and TP53 genes have been subjected to diagnostic and therapeutic applications (Toloza et al, 2006; Herbst et al, 2008); therefore, identification of more genes involved in lung carcinogenesis will be highly applicable to further improve the diagnosis and therapy of lung cancer. Allelic imbalance (AI) studies on lung cancer have identified several chromosome arms frequently hemizygously deleted, such as 1p, 4q, 5q, 6q, 8p, 11q, 12q, 13q, 17q, and 21q (Shiseki et al, 1996; Kawanishi et al, 1997; Virmani et al, 1998; Girard et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

A catalog of genes homozygously deleted in human lung cancer and the candidacy of PTPRD as a tumor suppressor gene

Kohno¹,

Otsuka²,

Girard³

et al. 2010

Genes Chromosomes & Cancer

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A total of 176 genes homozygously deleted in human lung cancer were identified by DNA array-based whole genome scanning of 52 lung cancer cell lines and subsequent genomic PCR in 74 cell lines, including the 52 cell lines scanned. One or more exons of these genes were homozygously deleted in one (1%) to 20 (27%) cell lines. These genes included known tumor suppressor genes, e.g., CDKN2A/p16, RB1, and SMAD4, and candidate tumor suppressor genes whose hemizygous or homozygous deletions were reported in several types of human cancers, such as FHIT, KEAP1, and LRP1B/LRP-DIP. CDKN2A/p16 and p14ARF located in 9p21 were most frequently deleted (20/74, 27%). The PTPRD gene was most frequently deleted (8/74, 11%) among genes mapping to regions other than 9p21. Somatic mutations, including a nonsense mutation, of the PTPRD gene were detected in 8/74 (11%) of cell lines and 4/95 (4%) of surgical specimens of lung cancer. Reduced PTPRD expression was observed in the majority (>80%) of cell lines and surgical specimens of lung cancer. Therefore, PTPRD is a candidate tumor suppressor gene in lung cancer. Microarray-based expression profiling of 19 lung cancer cell lines also indicated that some of the 176 genes, such as KANK and ADAMTS1, are preferentially inactivated by epigenetic alterations. Genetic/epigenetic as well as functional studies of these 176 genes will increase our understanding of molecular mechanisms behind lung carcinogenesis.

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Section: Introductionmentioning

confidence: 99%

A catalog of genes homozygously deleted in human lung cancer and the candidacy of PTPRD as a tumor suppressor gene

Kohno¹,

Otsuka²,

Girard³

et al. 2010

Genes Chromosomes & Cancer

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“…Lung cancer is the leading cause of cancer-related deaths in men and women in the United States [1]. It has a high mortality because it is difficult to detect early and is frequently resistant to available chemotherapy and radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

Deletion of Forkhead Box M1 Transcription Factor from Respiratory Epithelial Cells Inhibits Pulmonary Tumorigenesis

et al. 2009

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The Forkhead Box m1 (Foxm1) protein is induced in a majority of human non-small cell lung cancers and its expression is associated with poor prognosis. However, specific requirements for the Foxm1 in each cell type of the cancer lesion remain unknown. The present study provides the first genetic evidence that the Foxm1 expression in respiratory epithelial cells is essential for lung tumorigenesis. Using transgenic mice, we demonstrated that conditional deletion of Foxm1 from lung epithelial cells (epFoxm1−/− mice) prior to tumor initiation caused a striking reduction in the number and size of lung tumors, induced by either urethane or 3-methylcholanthrene (MCA)/butylated hydroxytoluene (BHT). Decreased lung tumorigenesis in epFoxm1−/− mice was associated with diminished proliferation of tumor cells and reduced expression of Topoisomerase-2α (TOPO-2α), a critical regulator of tumor cell proliferation. Depletion of Foxm1 mRNA in cultured lung adenocarcinoma cells significantly decreased TOPO-2α mRNA and protein levels. Moreover, Foxm1 directly bound to and induced transcription of the mouse TOPO-2α promoter region, indicating that TOPO-2α is a direct target of Foxm1 in lung tumor cells. Finally, we demonstrated that a conditional deletion of Foxm1 in pre-existing lung tumors dramatically reduced tumor growth in the lung. Expression of Foxm1 in respiratory epithelial cells is critical for lung cancer formation and TOPO-2α expression in vivo, suggesting that Foxm1 is a promising target for anti-tumor therapy.

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“…Actually, in breast cancer progression and metastasis, OPN is known as an important mediator, and it has been investigated as a potential therapeutic target in the treatment of breast cancer [34]. Patients of breast cancer suffering metastasis to the lung are faced with limited treatment options [35]. Since secreted phosphoproteins are readily accessible in the extracellular environment, OPN has gained much attention as an attractive therapeutic target for the blockade of tumor growth and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Aerosol Delivery of Small Hairpin Osteopontin Blocks Pulmonary Metastasis of Breast Cancer in Mice

Minai-Tehrani

Chang

et al. 2010

PLoS ONE

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BackgroundMetastasis to the lung may be the final step in the breast cancer-related morbidity. Conventional therapies such as chemotherapy and surgery are somewhat successful, however, metastasis-related breast cancer morbidity remains high. Thus, a novel approach to prevent breast tumor metastasis is needed.Methodology/Principal FindingAerosol of lentivirus-based small hairpin osteopontin was delivered into mice with breast cancer twice a week for 1 or 2 months using a nose-only inhalation system. The effects of small hairpin osteopontin on breast cancer metastasis to the lung were evaluated using near infrared imaging as well as diverse molecular techniques. Aerosol-delivered small hairpin osteopontin significantly decreased the expression level of osteopontin and altered the expression of several important metastasis-related proteins in our murine breast cancer model.Conclusion/SignificanceAerosol-delivered small hairpin osteopontin blocked breast cancer metastasis. Our results showed that noninvasive targeting of pulmonary osteopontin or other specific genes responsible for cancer metastasis could be used as an effective therapeutic regimen for the treatment of metastatic epithelial tumors.

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Gene therapy for lung cancer

Cited by 26 publications

References 94 publications

A catalog of genes homozygously deleted in human lung cancer and the candidacy of PTPRD as a tumor suppressor gene

A catalog of genes homozygously deleted in human lung cancer and the candidacy of PTPRD as a tumor suppressor gene

Deletion of Forkhead Box M1 Transcription Factor from Respiratory Epithelial Cells Inhibits Pulmonary Tumorigenesis

Aerosol Delivery of Small Hairpin Osteopontin Blocks Pulmonary Metastasis of Breast Cancer in Mice

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