A circulating tumor cell (CTC) cluster
A circulating tumor cell (CTC) cluster stained for keratin (red) and proliferation marker (green) (Image courtesy of the Yu Lab)

In the war against cancer, metastasis is one of the most difficult problems due to its complex nature: metastasis can have a very early onset, it may remain dormant for a long time and it also evolves during treatment. The complex process of metastatic cascade is still poorly understood, and there are a lack of therapies targeting metastatic spread.

Distant metastasis is mostly initiated by tumor cells shed from the primary tumor into the blood circulation and carried to distant organs where metastatic tumors eventually arise. Being able to seed on a distant organ and initiate a new tumor growth, circulating tumor cells (CTCs) are believed to contain cancer stem cells. Advances in technologies have allowed us to be able to isolate the CTCs from cancer patients. However, their biological properties are still largely undefined.

Our lab is interested in identifying the cancer stem cells from the CTCs and developing new therapeutic approaches for targeting the metastatic tumor initiating cells.

We will be focusing on the following major questions:

  1. What proportions of the cells in CTCs are cancer stem cells and how are they molecularly different from other cells? Cancer stem cells are defined as being able to self renew, differentiate into other type of tumor cells and initiate tumor growth. We will utilize the CTCs isolated from the luminal subtype of breast cancers from patients and mouse models to characterize those properties in cell culture and in animals, combing imaging, cell tracing, limited dilution and expression profiling.
  2. What are the microenvironmental cues that facilitate tumor growth in metastatic sites? The previously proposed “seed and soil” theory in metastasis has suggested that there are specific microenvironmental niches from the host organs that promote the growth of tumor cells. In collaborations with bioengineering experts, we will take advantages of bioengineering inventions to test and analyze different factors that promote CTCs growth in vitro and in vivo.
  3. Can we target the metastatic initiating cells? We will explore the consequences of targeting the candidate metastatic promoting genes identified from CTCs in patients, using in vitro and xenografted tumor models. The approaches include the RNAi mediated silencing, small molecule inhibitors and combination with potential nanoparticle-mediated deliveries.