Distant metastasis is initiated by circulating tumor cells (CTCs), which are considered to be a determining factor for the degree of metastasis and the survival of cancer patients. Although CTC-based diagnostic approaches are being rapidly developed, limited studies have proven the benefits of CTC elimination, with most studies providing only hypothetical inference because of unpredictable nature and dynamics of CTCs.
We modified photodynamic therapy to specifically eliminate green fluorescent protein (GFP)-expressing CTCs and evaluated the therapeutic efficacy of CTC elimination via in vitro and in vivo experiments.
When circulating blood is illuminated with a blue laser (λ = 473 nm), the combination of GFP and photosensitizers induces a selective elimination of GFP-expressing CTCs, with limited effect on normal cells. In GFP-expressing cancer cell-infused mice model, numbers of circulating tumor cells were significantly reduced after blue laser illumination. In GFP-expressing cancer cell transplanted mice models, the treatment suppressed distant metastasis and extended the survival of the tumor-bearing mice.
This study using novel photodynamic modality is the first experimental study to demonstrate that selective killing of CTCs delays distant metastasis significantly and ultimately improves survival. In addition, this study directly suggests CTCs are a core seed to be metastasized into secondary organs.
Clinical trial identification
Legal entity responsible for the study
Kyung Hee University.
National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (HA17C0039) Kyung Hee University (KHU-20170844).
Y.R. Kim: CEO: Oncocross. All other authors have declared no conflicts of interest.