Graphene disrupts signals on cancer stem cell membrane.
Image credit: K. Novoselov/University of Manchester
Cancer stem cells are precursor cells that can self-renew and differentiate into cancer cells and form tumors. Conventional treatments like chemotherapy and radiotherapy that wipe out the bulk of cancer cells don't always kill cancer stem cells - a residue can survive and grow.
Residual cancer stem cells drive tumor recurrence and metastasis - where cancer spreads to other parts of the body. Metastasis is responsible for 90% of cancer deaths, so any treatment that prevents it will make a huge difference to patient survival.
Cancer stem cells are also thought to drive drug resistance, causing a significant problem for the effective treatment of cancer.
Now, a new study suggests that graphene - a nanomaterial made of extremely thin flakes of carbon that are only one atom thick - may prove to be effective in eliminating cancer stem cells.
Reporting in the journal Oncotarget, a team from the University of Manchester in the UK led by Michael Lisanti, a professor in Manchester's Institute of Cancer Sciences - describes how graphene oxide - a modified version of graphene - selectively targeted cancer stem cells in a range of cancers.
The researchers suggest their findings open the possibility of using graphene with existing treatments not only to shrink tumors but also to prevent recurrence and metastasis.
Graphene oxide flakes prevented cancer stem cells forming tumor-spheres
The team became interested in graphene - in the form of graphene oxide - because it has shown potential as a carrier for drug delivery. The material is stable in water, and readily attaches itself to cell surfaces.
But co-author Dr. Aravind Vijayaraghavan, of Manchester's School of Materials and National Graphene Institute, says they were surprised to find that it is the graphene oxide itself that appears to be an effective anticancer drug. He explains:
"Cancer stem cells differentiate to form a small mass of cells known as a tumor-sphere. We saw that the graphene oxide flakes prevented CSCs [cancer stem cells] from forming these, and instead forced them to differentiate into noncancer stem cells."
However, while he and his colleagues hope these early results will lead to new cancer treatments, they also caution that there is a lot of work to do before graphene is ready for clinical trials with cancer patients.
Graphene was effective against six different cancer types
For the study, the team tested a range of graphene oxide formulations of different flake sizes on cancer stem cells from six types of cancer: breast, pancreatic, lung, brain, ovarian and prostate.
They used a method that is commonly used to test cancer stem cells, called the tumor-sphere assay or test. In the test, a tumor-sphere - a solid spherical, fused mass of cells - develops from a single cancer stem cell. Tumor spheres arising from cancer stem cells are easy to differentiate from clumps of other types of cell.
The researchers found the graphene oxide flakes prevented cancer stem cells from forming tumor-spheres across all six types of cancer, suggesting the method could work for a large range of cancers.
Further investigation revealed that graphene oxide prevents cancer stem cells from forming tumor-spheres by inhibiting several important signal pathways on the cells' surfaces.
The team suggests the results show graphene has potential use in combination therapy, helping to boost results of conventional treatments. Co-author Dr. Federica Sotgia, also of Manchester's Institute of Cancer Sciences, concludes:
"These findings show that graphene oxide could possibly be applied as a lavage or rinse during surgery to clear CSCs or as a drug targeted at CSCs."
The study builds on the pioneering work of two Manchester University physicists - Andre Geim and Kostya Novoselov - who won the Nobel Prize in Physics after successfully isolating graphene from graphite in 2004.
Meanwhile, Medical News Today recently learned of another study where a team showed that camel antibodies can ferry anticancer viruses directly to tumor cells. The findings raise the hope of developing effective gene therapies that target specific cell types.