Projects / Programmes
Evaluation of the mulitdrug resistance gene expression in the small cell lung cancer (SCLC) patients before treatment and after relapse: a need for the improvement of the SCLC therapy
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| B790 |
Biomedical sciences |
Clinical genetics |
small cell lung cancer , gene expression, multidrug resistance proteins
Researchers (2)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
18299 |
PhD Urška Čegovnik Primožič |
Biochemistry and molecular biology |
Researcher |
2005 - 2009 |
0 |
| 2. |
10921 |
PhD Mitja Košnik |
Microbiology and immunology |
Head |
2005 - 2009 |
0 |
Organisations (1)
Abstract
The acquired resistance of lung cancer to anticancer drugs is a serious clinical problem. The MDR phenotype is mainly caused by drug transport from the cell mediated by ABC transporters (multidrug resistance proteins). The purpose of this study was to measured multidrug resistance gene expression profile in the primary tumor and dislocated metastasis, to establish clinical and prognostic importance of the MDR markers and to examine the mechanisms of the acquired drug resistance in small cell lung cancer patients.
Significance for science
In this study we evaluate the mRNA expression levels of P-gp, MRP1, BCRP, LRP and topoisomerase II? in SCLC and NSCLC metastatic cells. To our knowledge, this is the first study to compare the mRNA expression levels of those markers in SCLC and NSCLC in chemo-naive metastatic cells to the benefits of chemotherapy, response to cytotoxic agents and overall survival. The mediastinal lymph node sampling helped us to overcome the errors contributed to the contamination of tumour tissue with epithelial tissue because it has been previously reported that ABC transporters along with topoisomerase II? are also expressed in healthy tissue. This approach should be also feasible for studying of other genes which are important for survival and spreading of metastatic cells. Our results demonstrated higher expression levels of the multidrug associated factor BCRP as well as much lower levels of topoisomerase II? in chemo-naive metastatic cells in NSCLC than in SCLC. Hence, we demonstrated that SCLC at the beginning of chemotherapy is potentially more sensitive to chemotherapeutic agents while in NSCLC resistance is usually inherent. We further showed that altered levels of topoisomerase II? and BCRP in SCLC are important factors that contribute to resistance to chemotherapeutics that interfere with the enzyme and/or DNA and are highly associated with overall survival. Topoisomerase and BCRP appear to be good markers for determining the outcome of the treatment and length of overall survival. Based on the expression levels of the enzyme and the transporter, appropriate therapy regimens that are better suited to each individual could be selected
Significance for the country
Despite recent advantages in the management of early disease and biological drugs, lung cancer remains the most commonly diagnosed cancer and the most common cause of death worldwide. In lung cancer management, surgery and radiation play an important role, but chemotherapy is crucial for the treatment of small cell lung cancer (SCLC) and is increasingly used in non-small cell lung cancer (NSCLC). However, resistance to chemotherapy is one of the most important therapeutic burdens for successful lung cancer therapy; therefore, a better understanding of drug resistance mechanisms is needed to improve survival of worldwide and Slovenian patients.
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