While well known for its unique electromechanical properties, graphene may also prove key in preventing cancer tumor recurrence. A drawback of traditional cancer treatment with radiation and chemotherapy is that the primary developmental source of future tumors is not eradicated. Cancer stem cells, or CSCs, can survive treatment and give rise to recurring tumors, metatasis, and drug resistance after repeated treatments. Researchers from the University of Manchester and the University of Calabria have discovered that graphene oxides targets and neutralize CSCs in a manner that is not yet fully understood.

One CSC can develop into a ball of new CSCs called a tumor-sphere, or into new tumor cells, such as what happens in metastasis. They're immortal, divide rapidly, and resist stress. A potential solution? Graphene oxide, GO, which is an oxidized form of its well-known carbon cousin and soluble in many solvents.

For a complete look at the efficacy of GO across cancers, researchers used CSCs from six types of cancer: breast, pancreatic, lung, brain, ovarian and prostate. They also used normal skin cells to confirm that GO would not be toxic to the body.

After cells were treated for 48 hours with a GO solution, the researchers found that not only did GO interrupt the ability of CSCs in all cancer types to proliferate by forming spheres, but that GO was safe to the skin cells.

Dr Aravind Vijayaraghavan of the National Graphene Institute at the University of Manchester says that GO seems to force the cancer stem cells to differentiate into non-cancer stem cells. In this way, GO effectively takes the CSC out of commission for creating future tumors. Currently the theory is that GO interferes with the signalling pathways in the cell membranes, curbing the proliferation mechanism.

Interestingly, this graphene derivative had already been researched for as a targeted delivery vehicle in tumors, but has now been found to have an important effect itself on the tumor.

While the researchers acknowledge that the mechanisms at play need to be researched more before the material can be used to treat cancers, the ability to destroy cancer stem cells is an an important component of a cancer treatment protocol that kills existing tumors as well as shuts down future metatasis.

Vijayaraghavan and the Graphene Institute have previously made headlines as a recipient of research money from the Bill and Melinda Gates Foundation towards the development of a better condom. Their proposal, of course, used graphene.

The team's research was originally published in Oncotarget on February 24, 2015.

Source: University of Manchester

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Graphene derivative interferes with seemingly invincible cancer stem cells

H. Lee Moffitt Cancer Center & Research Institute

TAMPA, Fla. - Glioblastomas are a highly aggressive type of brain tumor, with few effective treatment options. Moffitt Cancer Center researchers are one step closer to understanding glioblastoma development following the identification of a key protein signaling pathway involved in brain tumor stem cell growth and survival. Brain tumor stem cells are believed to play an important role in glioblastoma development and may be possible therapeutic targets.

The neurotrophin protein pathway controls nerve growth, survival and specialization. In an article published in the Feb. 6 issue of The Journal of Biological Chemistry, Moffitt researchers reported that the neurotrophin pathway is also involved in the survival and growth of brain tumor stem cells. The stem cells have high levels of neurotrophin receptors called TrkB and TrkC. Cellular signals from normal brain cells can activate TrkB and TrkC on the stem cells and stimulate cell growth. And when scientists inhibited TrkB and TrkC, they found decreased stem cell survival. This suggests that TrkB and TrkC may be possible drug targets for stem cells in gliomas and glioblastomas.

"This work might be a first step in developing new treatment approaches targeting brain tumor stem cells. It may also partly explain why brain tumors can grow so quickly since proteins from the surrounding normal brain might be used by the tumor to grow even faster," said Peter A. Forsyth, M.D., chair of the Department of Neuro-Oncology at Moffitt.

Researchers also reported a potential reason why several clinical trials targeting a protein called EGFR in glioblastoma patients have failed to live up to expectations. EGFR is frequently activated in glioblastoma, but results from trials using EGFR inhibitors showed little or no patient improvement. Moffitt scientists discovered that TrkB and TrkC maintain brain stem cell survival and growth even when EGFR inhibitors are used. These observations suggest that one reason why EGFR inhibitors may be ineffective in glioblastoma is that TrkB and TrkC are active, thereby bypassing EGFR inhibition and allowing stem cells to continue to grow.

This is the first time that scientists have shown that TrkB and TrkC are involved in brain tumor stem cell growth. Currently, no drugs that target TrkB and TrkC have been used as brain cancer treatments. Researchers hope that these results might encourage the development of drugs that target both the stem cell compartment and the more differentiated parts of the brain tumor and result in more effective therapies.

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The study was supported by funds The V Foundation for Cancer Research and the Moffitt Cancer Center Foundation.

About Moffitt Cancer Center:

Located in Tampa, Moffitt is one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt's excellence in research, its contributions to clinical trials, prevention and cancer control. Moffitt is the top-ranked cancer hospital in the Southeast and has been listed in U.S. News & World Report's "Best Hospitals" for cancer care since 1999. With more than 4,500 employees, Moffitt has an economic impact in Florida of nearly $1.6 billion. For more information, visit MOFFITT.org, and follow the Moffitt momentum on Facebook, Twitter and YouTube.

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Moffitt researchers identify protein pathway involved in brain tumor stem cell growth

Bioengineers from Brigham and Women's Hospital (BWH) with collaborators at the pharmaceutical company Sanofi have identified small molecules that can be used to program stem cells to home in on sites of damage, disease and inflammation. The techniques used to find and test these small molecules may represent important tools in advancing cell-based therapy, offering a new strategy for delivering cells to the right locations in the body. The results of their work appear online this week in Cell Reports.

Through a collaborative research project, the research team tested more than 9,000 compounds, and used a multi-step approach -- including a sophisticated microfluidics set up and novel imaging technique -- to narrow in on and test the most promising compounds.

"There are all kinds of techniques and tools that can be used to manipulate cells outside of the body and get them to do almost anything we want, but once we transplant cells we lose complete control over them," said co-senior author Jeff Karp, PhD, an associate professor at BWH, Harvard Medical School, and principal faculty at the Harvard Stem Cell Institute. "Through this collaboration, we've been able to identify small molecules that can be used to treat cells outside of the body, programming them to target blood vessels in diseased or damaged tissue."

Small molecules offered the team several advantages including the ability to use a safe and relatively simple procedure to pre-treat the cells before injecting them intravenously.

"There's a great need to develop strategies that improve the clinical impact of cell-based therapies," said co-first author Oren Levy, PhD, an instructor in medicine at BWH. "If you can create an engineering strategy that is safe, cost effective and simple to apply, that's exactly what we need to achieve the promise of cell-based therapy."

Karp's team at the Brigham had previously found that it is possible to use bioengineering techniques to chemically attach molecules to the surface of a cell that act as a GPS, guiding the cell to the site of inflammation. These findings indicated that targeted delivery of cells was possible, but a scalable approach would be needed to impact patients.

"At BWH, we had laid the groundwork. Our collaborators at Sanofi have complementary expertise in screening for small molecules, deep understanding of the biology and unmet needs, and an exceptional ability to bring new therapeutics to the clinic," said Karp. "Defined goals and both teams working seamlessly together created perfect synergy. We learned so much from each other."

The Sanofi team screened thousands of compounds, looking for ones that activated telltale molecules on the surface of the MSCs, as well as verified that the active compounds did not alter mesenchymal stromal cell viability or the profile of secreted immunomodulatory protein factors.

There are currently more than 450 clinical trials ongoing or completed using mesenchymal stem cells (MSCs) to treat a range of diseases including heart attacks, Crohn's disease, lupus, multiple sclerosis and more, but many trials fail to meet clinical endpoints. One of the key challenges has been getting MSCs to arrive at -- and stay at -- sites of damage.

Researchers found six promising molecules, including one known as Ro-31-8425, the most potent of the group. Karp's lab then tested these compounds further by pre-treating cells with them, and then flowed the cells onto a microfluidic device -- a glass slide with tiny channels only big enough to allow small groups of cells to flow through at a time. The channels were coated with an Intracellular Adhesion Molecule (ICAM-1), which is also found on the surface of blood vessels at inflamed tissue within the body. Cells pre-treated with Ro-31-8425 stuck -- a sign that they might be able to home in on sites of inflammation.

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Small molecule helps get stem cells to sites of disease, damage