Detection of circulating tumour cell clusters in human glioblastoma.

Krol I; Castro-Giner F; Maurer M; Gkountela S; Szczerba BM; Scherrer R; Coleman N; Carreira S; Bachmann F; Anderson S; Engelhardt M; Lane H; Evans TRJ; Plummer R; Kristeleit R; Lopez J; Aceto N

doi:10.1038/s41416-018-0186-7

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Journal article

Detection of circulating tumour cell clusters in human glioblastoma.

Krol I Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, CH-4058, Basel, Switzerland.
Castro-Giner F Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, CH-4058, Basel, Switzerland.
Maurer M Basilea Pharmaceutica International Ltd., CH-4058, Basel, Switzerland.
Gkountela S Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, CH-4058, Basel, Switzerland.
Szczerba BM Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, CH-4058, Basel, Switzerland.
Scherrer R Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, CH-4058, Basel, Switzerland.
Coleman N Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK.
Carreira S Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK.
Bachmann F Basilea Pharmaceutica International Ltd., CH-4058, Basel, Switzerland.
Anderson S Basilea Pharmaceutica International Ltd., CH-4058, Basel, Switzerland.
Engelhardt M Basilea Pharmaceutica International Ltd., CH-4058, Basel, Switzerland.
Lane H Basilea Pharmaceutica International Ltd., CH-4058, Basel, Switzerland.
Evans TRJ Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
Plummer R Northern Centre for Cancer Care, Newcastle upon Tyne, UK.
Kristeleit R University College London Cancer Institute, London, UK.
Lopez J Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, London, UK.
Aceto N Department of Biomedicine, Cancer Metastasis Laboratory, University of Basel and University Hospital Basel, CH-4058, Basel, Switzerland. Nicola.Aceto@unibas.ch.

2018-08-02

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British journal of cancer. - 2018

Xenograft Model Antitumor Assays

English Human glioblastoma (GBM) is a highly aggressive, invasive and hypervascularised malignant brain cancer. Individual circulating tumour cells (CTCs) are sporadically found in GBM patients, yet it is unclear whether multicellular CTC clusters are generated in this disease and whether they can bypass the physical hurdle of the blood-brain barrier. Here, we assessed CTC presence and composition at multiple time points in 13 patients with progressing GBM during an open-label phase 1/2a study with the microtubule inhibitor BAL101553. We observe CTC clusters ranging from 2 to 23 cells and present at multiple sampling time points in a GBM patient with pleomorphism and extensive necrosis, throughout disease progression. Exome sequencing of GBM CTC clusters highlights variants in 58 cancer-associated genes including ATM, PMS2, POLE, APC, XPO1, TFRC, JAK2, ERBB4 and ALK. Together, our findings represent the first evidence of the presence of CTC clusters in GBM.

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