Initiation and characterization of small cell lung cancer patient-derived xenografts from ultrasound-guided transbronchial needle aspirates

Small cell lung cancer (SCLC) is a devastating disease with limited treatment options. Due to its early metastatic nature and rapid growth, surgical resection is rare. Standard of care treatment regimens remain largely unchanged since the 1980's, and five-year survival lingers near 5%. Patient-...

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Bibliographic Details
Published in:PloS one 2015-05, Vol.10 (5), p.e0125255-e0125255
Main Authors: Anderson, Wade C, Boyd, Michael B, Aguilar, Jorge, Pickell, Brett, Laysang, Amy, Pysz, Marybeth A, Bheddah, Sheila, Ramoth, Johanna, Slingerland, Brian C, Dylla, Scott J, Rubio, Edmundo R
Format: Article
Language:English
Subjects:
Animal models
Animal tissues
Animals
Antigens, Neoplasm - immunology
Biology
Biomarkers, Tumor - metabolism
Biopsy, Fine-Needle
Breast cancer
Bronchi - diagnostic imaging
Bronchi - pathology
Cancer
Cancer therapies
Chemotherapy
Cisplatin
Colorectal cancer
Critical care
Cryopreservation
Disease control
Etoposide
Experimentation
Histology
Humans
Immunohistochemistry
Lung cancer
Lung diseases
Lung Neoplasms - diagnostic imaging
Lung Neoplasms - pathology
Medical diagnosis
Medical personnel
Medical research
Medical treatment
Medicine
Metastases
Mice
Middle Aged
Patients
Physicians
R&D
Research & development
Research institutions
Shipping
Small cell lung cancer
Small cell lung carcinoma
Small Cell Lung Carcinoma - diagnostic imaging
Small Cell Lung Carcinoma - pathology
Stem cells
Studies
Surgery
Treatment Outcome
Tumors
Ultrasonic imaging
Ultrasonography
Ultrasound
Xenograft Model Antitumor Assays
Xenografts
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Summary:Small cell lung cancer (SCLC) is a devastating disease with limited treatment options. Due to its early metastatic nature and rapid growth, surgical resection is rare. Standard of care treatment regimens remain largely unchanged since the 1980's, and five-year survival lingers near 5%. Patient-derived xenograft (PDX) models have been established for other tumor types, amplifying material for research and serving as models for preclinical experimentation; however, limited availability of primary tissue has curtailed development of these models for SCLC. The objective of this study was to establish PDX models from commonly collected fine needle aspirate biopsies of primary SCLC tumors, and to assess their utility as research models of primary SCLC tumors. These transbronchial needle aspirates efficiently engrafted as xenografts, and tumor histomorphology was similar to primary tumors. Resulting tumors were further characterized by H&E and immunohistochemistry, cryopreserved, and used to propagate tumor-bearing mice for the evaluation of standard of care chemotherapy regimens, to assess their utility as models for tumors in SCLC patients. When treated with Cisplatin and Etoposide, tumor-bearing mice responded similarly to patients from whom the tumors originated. Here, we demonstrate that PDX tumor models can be efficiently established from primary SCLC transbronchial needle aspirates, even after overnight shipping, and that resulting xenograft tumors are similar to matched primary tumors in cancer patients by both histology and chemo-sensitivity. This method enables physicians at non-research institutions to collaboratively contribute to the rapid establishment of extensive PDX collections of SCLC, enabling experimentation with clinically relevant tissues and development of improved therapies for SCLC patients.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0125255