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

PLoS One. 2015 May 8;10(5):e0125255. doi: 10.1371/journal.pone.0125255. eCollection 2015.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Biomarkers, Tumor / metabolism
  • Biopsy, Fine-Needle
  • Bronchi / diagnostic imaging*
  • Bronchi / pathology*
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / pathology*
  • Mice
  • Middle Aged
  • Small Cell Lung Carcinoma / diagnostic imaging*
  • Small Cell Lung Carcinoma / pathology*
  • Treatment Outcome
  • Ultrasonography
  • Xenograft Model Antitumor Assays*

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor

Grant support

WCA, JA, BP, AL, MAP, SB, JR, BCS, and SJD are employees of Stem CentRx, Inc., a biotechnology company focused on therapeutic targeting of Cancer Stem Cells. The funder provided support in the form of salaries for authors WCA, JA, BP, AL, MAP, SB, JR, BCS, and SJD, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.