Abstract B054: Impairing the reseeding of circulating tumor cells decelerates metastatic progression
| Autor: | Chen Qian, Fei Shen, Olimpia Meucci, Alessandro Fatatis, Joseph M. Salvino, Asurayya Worrede-Mahdi |
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| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | Molecular Cancer Therapeutics. 17:B054-B054 |
| ISSN: | 1538-8514 1535-7163 |
| DOI: | 10.1158/1535-7163.targ-17-b054 |
| Popis: | This study aims to understand the mechanisms and dynamics by which cancer cells, departing from existing metastases as circulating cancer cells (CTCs), further seed and colonize skeleton and soft tissues, expanding metastatic spreading and precipitating the clinical progression to terminal disease. We have previously shown that the chemokine receptor CX3CR1 is implicated in the metastatic seeding of breast cancer cells and that FX-68, a novel small-molecule antagonist for this receptor, effectively contains both number of lesions and total tumor burden in animal models of metastatic disease. Here we established that FX-68 impairs the reseeding of skeleton and soft-tissue and that the CTCs unable to reseed and forced to remain in the blood eventually succumb to apoptotic death. The metastatic potential of CTCs was confirmed by reinoculation experiments as well as by forcefully mobilizing cancer cells from metastases back in the blood and assessing the number of additional lesions generated, in the presence and absence of FX-68. Finally, we hypothesized that prolonging the permanence of CTCs in the blood could improve their exposure to chemotherapy drugs. This paradigm was tested by combining FX-68 with doxorubicin or docetaxel and assessing drug bioavailability and antimetastatic effects. In summary, our results strongly support developing CX3CR1 antagonists and promoting their clinical use, as this approach will provide novel and effective tools to contain the progression of metastatic disease in patients. Citation Format: Chen Qian, Asurayya Worrede-Mahdi, Fei Shen, Joseph Salvino, Olimpia Meucci, Alessandro Fatatis. Impairing the reseeding of circulating tumor cells decelerates metastatic progression [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B054. |
| Databáze: | OpenAIRE |
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