Key Characteristics of Circulating Tumor Cell Clusters and Implications for Cancer Metastases


  • Yakov Perlov Belmont High School
  • Dean Lee Scientist in HiFiBiO Therapeutics, a local (Cambridge) biotechnology company



Cancer, Circulating Tumor Cells, CTC, Circulating Tumor Cell Clusters, Chemotherapy, Chemoresistance, Apoptosis, Anoikis, Reduced Apoptosis, Necrosis, Quiescence, Stemness, Cancer Stem Cells, CSCs, Cancer Epigenetics, Polycomb, Tumor Spheroids, Tumorospheres, CTC Clusters, Single CTCs, Metastasis


Primary tumors generate metastases by shedding tumor cells into the circulation; these circulating tumor cells (CTCs) implant at distant sites to develop into metastatic lesions. CTCs can travel either as clusters or as single CTCs. Previous studies revealed that the frequency of CTC clusters in a cancer patient positively correlates with the likelihood of developing metastatic lesions. Three key characteristics of CTC clusters - chemoresistance, reduced apoptosis, and epigenetically programmed stemness - enhance their metastatic potential relative to single CTCs:

  1. CTC clusters seem to be more resistant to chemotherapy due to their quiescent and necrotic cores, making drug penetration difficult. Their chemoresistance also correlates with specific molecular components of the extracellular matrix.

  2. CTC clusters suffer lower rates of apoptosis. This might be attributed to autocrine factors that protect against immune attack and the epithelial-mesenchymal transition.

  3. The DNA methylation landscape of CTC clusters closely resembles that of embryonic stem cells. It features hypomethylation of four critical transcription factors associated with stemness and hypermethylation of a set of pro-differentiation genes.

Further research might focus on the interdependence of these three characteristics and whether they precede or follow the clustering of CTCs. The answers to these research questions will help drug developers define specific mechanisms that can curb the metastatic potential of CTC clusters.


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Author Biographies

Yakov Perlov, Belmont High School

Yakov is a senior from Belmont, Massachusetts. Yakov is focused on cancer research and has a niche interest in the steps leading up to cancer metastasis, such as the epithelial-mesenchymal transition. He hopes to continue his studies in the life sciences at the undergraduate and graduate levels.

Dean Lee, Scientist in HiFiBiO Therapeutics, a local (Cambridge) biotechnology company

Dean is a scientist for computational biology at HiFiBiO Therapeutics. He collaborates with immunologists and cancer biologists to discover and validate promising targets for antibody-based drugs. He is interested in using classical machine learning methods as well as newly described deep learning methods to better mine large genomics and transcriptomics datasets.

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How to Cite

Perlov, Y., & Lee, D. (2021). Key Characteristics of Circulating Tumor Cell Clusters and Implications for Cancer Metastases. Journal of Student Research, 10(2).



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