Abstract 3060: Circulating tumor cells from small cell lung cancer patients are tumorigenic
Authors: Morrow Christopher J. , Hodgkinson Cassandra L. , Li Yaoyong , Metcalf Robert , Rothwell Dominic , Trapani Francesca , Polanski Radoslaw , Burt Debbie , Simpson Kathryn , Morris Karen , Pepper Stuart , Nonaka Daisuke , Greystole Alastair , Kelly Paul , Krebs Matthew , Antonello Jenny , Ayub Mahmood , Faulkner Suzanne , Priest Lynsey , Carter Louise , Tate Catriona , Miller Crispin J. , Blackhall Fiona , Brady Ged , Dive Caroline 
Published: May 2015

Small cell lung cancer (SCLC), is a highly aggressive and metastatic disease with a 5 year survival of 5%. SCLC represents 15-20% of all lung cancers and causes &gt;160,000 deaths a year. The majority of patients present with metastatic disease and consequently resections are rare, while biopsies are small and only for diagnostic purposes thus hampering the study of SCLC. However, circulating tumour cells (CTCs) are highly prevalent in SCLC patients and may represent an avenue for the better understanding this disease. Our aim was to determine whether CTCs isolated from SCLC patients were able to form tumours in immunocompromised mice. This was accomplished by erythrocyte and leukocyte depletion and implantation of the remaining cells. Of the 6 initial patients whose CTCs were implanted, 4 gave rise to tumours in less than 5 months. Immuno-histochemical analysis of the tumours revealed them to be human in nature and express markers consistent with SCLC. Whole exome sequencing demonstrated that the tumours had mutations (e.g. TP53 and RB1) and CNV (e.g. loss of 3p and 13q) commonly observed in SCLC samples. Furthermore, single cell analysis of CTCs isolated from the corresponding patient revealed that genetic abnormalities detected in the tumour were also present in the patients CTCs. This confirmed that the tumours (termed CDX for CTC derived explant), were indeed derived from CTCs. In all 4 successful cases, analysis of parallel blood samples by CellSearch demonstrated that the patients had more than 400 CTCs/7.5 ml blood. Two of these patients were initially sensitive to platinum/etoposide therapy, while 2 were refractory. The doubling times of CDX derived from refractory and sensitive patients were 7.2 and 5.0 days compared to 14.2 and 13.4 days, consistent with refractory SCLC being more aggressive than sensitive SCLC. We have been able to successfully passage, freeze and resurrect all the CDX models and aim to report whether the patient response to therapy is mirrored in their CDX. These data demonstrate that SCLC CTCs are tumorigenic and we are investigating whether the CTC derived tumours represent a faithful model of the clinical disease.

Citation Format: Christopher J. Morrow, Cassandra L. Hodgkinson, Yaoyong Li, Robert Metcalf, Dominic Rothwell, Francesca Trapani, Radoslaw Polanski, Debbie Burt, Kathryn Simpson, Karen Morris, Stuart Pepper, Daisuke Nonaka, Alastair Greystole, Paul Kelly, Matthew Krebs, Jenny Antonello, Mahmood Ayub, Suzanne Faulkner, Lynsey Priest, Louise Carter, Catriona Tate, Crispin J. Miller, Fiona Blackhall, Ged Brady, Caroline Dive. Circulating tumor cells from small cell lung cancer patients are tumorigenic. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3060. doi:10.1158/1538-7445.AM2014-3060