Cultured circulating tumor cells and their derived xenografts for personalized oncology

Abstract

Recent cancer research has demonstrated the existence of circulating tumor cells (CTCs) in cancer patient's blood. Once identified, CTC biomarkers will be invaluable tools for clinical diagnosis, prognosis and treatment. In this review, we propose ex vivo culture as a rational strategy for large scale amplification of the limited numbers of CTCs from a patient sample, to derive enough CTCs for accurate and reproducible characterization of the biophysical, biochemical, gene expressional and behavioral properties of the harvested cells. Because of tumor cell heterogeneity, it is important to amplify all the CTCs in a blood sample for a comprehensive understanding of their role in cancer metastasis. By analyzing critical steps and technical issues in ex vivo CTC culture, we developed a cost-effective and reproducible protocol directly culturing whole peripheral blood mononuclear cells, relying on an assumed survival advantage in CTCs and CTC-like cells over the normal cells to amplify this specified cluster of cancer cells.

The Prognostic Role of Circulating Tumor Cells (CTCs) in Lung Cancer

“…Short-term CTC culture (3–14 days) has been achieved in a number of cancer types, even from early stage cancers ( 137 – 139 ). This allows for the recapitulation of the disease in an ex vivo/in vivo setting for the testing of therapies and functional analysis ( 140 ).…”

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

“…Several important advances have been achieved in recent years, that have improved the potential of liquid biopsy markers as robust clinical tools. Such advances include (a) estimation of tumor mutational burden through evaluation of plasma cfDNA 200 ; (b) more therapy-directed applications of CTCs, for example, PD-L1 expression in CTCs 163,165,182 ; (c) use of CTCs as a longitudinal monitoring tool to detect minimal residual disease after curative surgery 171 ; (d) CTC-derived xenografts used as surrogates to study tumor biology [201][202][203] ; and (e) three-dimensional CTC cultures 204 and CTC-derived organoids to aid in individualized precision medicine. 205…”

Biology and therapy of urological cancer metastasis

“…Their model has the advantage over the other PDXs in that the bone metastatic tumor cells can grow in culture as well in situ generating both osteolytic and osteoblastic lesions in mouse skeleton in an anatomical regional-dependent manner. Taking advantage of their original success in establishing CTCs from mouse model of prostate cancer metastasis, Dr. Ruoxiang Wang [9] shared his views and experience on culturing CTCs in a highly reproducible manner to obtain CTCs and CTC-derived PDXs, or CDXs from cancer patients. CTCs/CDXs could become the first step of studying the mechanisms underlying cancer metastasis and to address the molecular basis of how therapeutic resistance to chemo- and hormonal-therapy may be developed.…”