Patient-derived xenografts of non-small-cell lung cancer: a pre-clinical model to evaluate adjuvant chemotherapy?
OBJECTIVE
Recent trials have evaluated adjuvant chemotherapy in patients with non-small-cell lung cancer (NSCLC). For stage IB to IIIA, a significant improvement of treatment results for platin-based chemotherapy was shown, but only one of the 20 patients treated has a benefit of disease-free and overall 5-year survival. In future the implementation of biomarkers, novel agents and individual selection may contribute to better treatment results in adjuvant therapy. Pre-clinical models are one way to study treatment innovations.


METHODS
We have developed a lung cancer xenograft model. Fresh tumour material of patients with NSCLC was subcutaneously transplanted to immunodeficient mice shortly after surgical resection. In total, 102 samples have been transplanted from which 25 passagable models could be generated. Of the established xenograft lines, 48% were derived from squamous cell carcinomas and 24% from adenocarcinomas. All but one originated from long-term smokers.


RESULTS
It could be shown that the early murine passages (maximum 10) were similar to the original tumour with regard to histology and the expression of the surface proteins as E-cadherin, EpCAM or the cell proliferation marker Ki-67. The growth rate of the established xenografts was a unique feature of the different models and not related to patient characteristics or to the histology type. All xenograft models showed a wide variability in response to both classical chemotherapy and targeted anti-epidermal growth factor receptor agents. Response rates were in good accordance with the results of recent clinical studies.


CONCLUSIONS
In summary, we have developed a panel of patient-derived NSCLC xenografts. These xenograft models could be used for pre-clinical studies to evaluate chemotherapy, novel targeted therapies and expression of potential biomarkers.
Merk
Johannes
J
Department of Thoracic Surgery, ELK Berlin Chest Hospital, Berlin, Germany. johannes.merk@elk-berlin.de
Rolff
Jana
J
Becker
Michael
M
Leschber
Gunda
G
Fichtner
Iduna
I
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000068818:Cetuximab; D017024:Chemotherapy, Adjuvant; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D011799:Quinazolines / Q000627:therapeutic use; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000068818:Cetuximab