Could Adjuvant Inhibition of Cancer Stem Cells Improve Local Therapy Outcomes?

Inhibition of cancer stem cells in hepatocellular carcinoma (HCC) may improve the efficacy of percutaneous thermal ablation, transarterial chemoembolization (TACE), and transarterial embolization (TAE), according to an abstract presented at the World Conference on Interventional Oncology.

Patients with HCC are often ineligible for transplant or resection, but certain patients are able to pursue a local cure through percutaneous thermal ablation or noncurative disease control with TACE or TAE. Recurrences of cancer after these treatments can occur as a result of incomplete ablation and are thought to be a result of cancer stem cells, which are resistant to typical therapies such as chemotherapy, radiation, percutaneous thermal ablation, and TACE.

For this study, the researchers hypothesized that administering HCC cancer stem cell inhibitors to HCC cell cultures exposed to conditions simulating incomplete PTA or TAE would decrease HCC cancer stem cell enrichment and HCC cell survival.

Three human HCC cell lines (Hep3B, PLC, and HepG2) were used in establishment of an incomplete percutaneous thermal ablation model. For 10 minutes, the cell lines were exposed to 46.5 °C water bath. A 37 °C water bath was used as control. To simulate TAE, cells were exposed for 72 hours to a 1% oxygen hypoxia chamber and serum-depleted medium.

The P13K pathway is often implicated in cancer stem cell signaling; therefore, the researchers treated cell cultures with P13K pathway inhibitor LY294002 and used DSMSO as a control. HCC cells that survived were evaluated using flow cytometry for the expression of stem cell markers EpCAM, CD133, and CD44.

Results indicated that several factors (sublethal heat, hypoxia, and starvation) led to increased expression of cancer stem cell markers, while cell lines exposed to cancer stem cell inhibitors showed a decrease in cancer stem cell populations.

“These data demonstrate that sublethal heat stress or hypoxia plus serum starvation induce an

enrichment of HCC cancer stem cells and that inhibition of HCC cancer stem cells reduces the CSC population. Future studies will focus on the mechanisms underlying cancer stem cell induction and inhibition in vitro and in vivo. If successful in vivo, adjuvant treatment with HCC cancer stem cell inhibitors could improve the efficacy of percutaneous thermal ablation, TACE and TAE,” the authors concluded.

Reference

Newton I, Huo Y. Towards improving thermal ablation and chemoembolization for hepatocellular carcinoma through cancer stem cell inhibition. Oral abstract presented at the World Conference on Interventional Oncology. June 2018. Boston, MA.