Circulating Tumor Cell-Derived Pre-Clinical Models for Personalized Medicine

Gabriel, Marta Tellez; Cochonneau, Denis; Cadé, Marie; Jubelin, Camille; Heymann, Marie-Françoise; Heymann, Dominique

doi:10.3390/cancers11010019

Cited by 55 publications

(49 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Drug-adapted cancer cell lines are, like every model system, associated with specific advantages and limitations. Models including primary cancer cell cultures, three-dimensional cell (co-) culture systems, tumour-derived organoids, and animal models better reflect certain aspects of tumour growth such as intra-tumour heterogeneity, three-dimensional architecture, cancer cell interaction with the cancer microenvironment, and/ or metastatic behaviour [105][106][107][108][109][110][111][112][113][114] . Such models can be used to study processes that cannot be studied in cell lines.…”

Section: Resultsmentioning

confidence: 99%

Drug-adapted cancer cell lines as preclinical models of acquired resistance

Michaelis¹,

Wass²,

Činátl³

2019

CDR

View full text Add to dashboard Cite

Acquired resistance formation limits the efficacy of anti-cancer therapies. Acquired and intrinsic resistance differ conceptually. Acquired resistance is the consequence of directed evolution, whereas intrinsic resistance depends on the (stochastic) presence of pre-existing resistance mechanisms. Preclinical model systems are needed to study acquired drug resistance because they enable: (1) in depth functional studies; (2) the investigation of non-standard treatments for a certain disease condition (which is necessary to identify small groups of responders); and (3) the comparison of multiple therapies in the same system. Hence, they complement data derived from clinical trials and clinical specimens, including liquid biopsies. Many groups have successfully used drug-adapted cancer cell lines to identify and elucidate clinically relevant resistance mechanisms to targeted and cytotoxic anti-cancer drugs. Hence, we argue that drug-adapted cancer cell lines represent a preclinical model system in their own right that is complementary to other preclinical model systems and clinical data.

show abstract

Section: Resultsmentioning

confidence: 99%

Drug-adapted cancer cell lines as preclinical models of acquired resistance

Michaelis¹,

Wass²,

Činátl³

2019

CDR

View full text Add to dashboard Cite

show abstract

“…These can be used for drug screening and can also be exploited to increase the number of cells available for a given analysis [13][14][15]. Nevertheless, their use for patient stratification is challenging, especially because the development of CTC-derived lines is a long and inefficient process (typically lasting several months), requires large numbers of cells, and is subject to possible biases during ex vivo culturing [16].…”

Section: Molecular Analysis Of Ctcsmentioning

confidence: 99%

Tracking cancer progression: from circulating tumor cells to metastasis

2020

View full text Add to dashboard Cite

The analysis of circulating tumor cells (CTCs) is an outstanding tool to provide insights into the biology of metastatic cancers, to monitor disease progression and with potential for use in liquid biopsy-based personalized cancer treatment. These goals are ambitious, yet recent studies are already allowing a sharper understanding of the strengths, challenges, and opportunities provided by liquid biopsy approaches. For instance, through single-cellresolution genomics and transcriptomics, it is becoming increasingly clear that CTCs are heterogeneous at multiple levels and that only a fraction of them is capable of initiating metastasis. It also appears that CTCs adopt multiple ways to enhance their metastatic potential, including homotypic clustering and heterotypic interactions with immune and stromal cells. On the clinical side, both CTC enumeration and molecular analysis may provide new means to monitor cancer progression and to take individualized treatment decisions, but their use for early cancer detection appears to be challenging compared to that of other tumor derivatives such as circulating tumor DNA. In this review, we summarize current data on CTC biology and CTC-based clinical applications that are likely to impact our understanding of the metastatic process and to influence the clinical management of patients with metastatic cancer, including new prospects that may favor the implementation of precision medicine. Publisher's NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

show abstract

“…In vivo models can be used to reveal the tumorigenic and metastatic phenotype of various CTC populations. The main difficulty lies in the fact that CTCs in the peripheral blood are represented by a low number of cells, and the technology of CTC transfer to in vitro and in vivo models is laborious [97]. Nonetheless, the development of cell lines from CTCs is still possible.…”

Section: In Vitro and In Vivo Study Of The Ctc Phenotypementioning

confidence: 99%

Heterogeneity of Circulating Tumor Cells in Breast Cancer: Identifying Metastatic Seeds

Menyailo

Tretyakova

Denisov

2020

IJMS

View full text Add to dashboard Cite

Metastasis being the main cause of breast cancer (BC) mortality represents the complex and multistage process. The entrance of tumor cells into the blood vessels and the appearance of circulating tumor cells (CTCs) seeding and colonizing distant tissues and organs are one of the key stages in the metastatic cascade. Like the primary tumor, CTCs are extremely heterogeneous and presented by clusters and individual cells which consist of phenotypically and genetically distinct subpopulations. However, among this diversity, only a small number of CTCs is able to survive in the bloodstream and to form metastases. The identification of the metastasis-initiating CTCs is believed to be a critical issue in developing therapeutic strategies against metastatic disease. In this review, we summarize the available literature addressing morphological, phenotypic and genetic heterogeneity of CTCs and the molecular makeup of specific subpopulations associated with BC metastasis. Special attention is paid to the need for in vitro and in vivo studies to confirm the tumorigenic and metastatic potential of metastasis-associating CTCs. Finally, we consider treatment approaches that could be effective to eradicate metastatic CTCs and to prevent metastasis. with partial EMT) and high metastatic potential [18,19]. In addition to the EMT features, CTCs can also exhibit stem-like characteristics, particularly self-renewal and multilineage differentiation ability [20].There is still no highly effective therapy for metastatic BC. Therapy targeted directly against CTCs seems to be promising. To date, various molecular markers of CTCs and their therapeutic targets that can be used to prevent cancer progression are known [21]. In addition, different therapeutic approaches for the elimination of CTCs have been proposed; however, none of them has been clinically approved. The reason is that the molecular and biological characteristics of the primary tumor and CTCs are not well understood. In our opinion, the main focus should be on the search for specific populations of CTCs responsible for the development of metastasis and the study of their molecular makeup. These cells could be the primary therapeutic target for preventing metastatic progression [22]. Recent advances in single-cell sequencing allow one to determine the population structure of CTCs and identify metastasis-initiating cells [23][24][25][26], while in vitro and in vivo studies provide data on their proliferative, apoptotic, invasive, and other phenotypes [27].Nowadays, despite a large number of studies on CTC heterogeneity and their metastatic potential, there are still no generally accepted and universal markers of CTCs prone to metastasis. In this review, we systematized the data on metastatic CTCs in terms of their morphological, phenotypic, and genetic heterogeneity in BC, as well as emphasized the importance of studying these cells in vitro and in vivo and developing therapeutic approaches for their elimination to prevent metastasis. CTC Heterogeneity and the Molecular Makeup...

show abstract

Circulating Tumor Cell-Derived Pre-Clinical Models for Personalized Medicine

Cited by 55 publications

References 116 publications

Drug-adapted cancer cell lines as preclinical models of acquired resistance

Drug-adapted cancer cell lines as preclinical models of acquired resistance

Tracking cancer progression: from circulating tumor cells to metastasis

Heterogeneity of Circulating Tumor Cells in Breast Cancer: Identifying Metastatic Seeds

Contact Info

Product

Resources

About