I was really sad when I heard about John McCain’s diagnosis with a glioblastoma, a particularly nasty type of brain tumor that we study in my lab when it shows up in children. My own battle with prostate cancer starting almost 8 years ago might have sensitized me to this news even though I’m in long-term remission. I also started thinking about whether stem cells could somehow help him fight or even beat the tumor. It turns out that others have been including stem cells in the mix in thinking about McCain’s treatment options.
How might stem cells be of use for patients like McCain with a serious brain tumor?
Many types of brain cancer have their own populations of stem cells that are called “cancer stem cells”, but it turns out that other stem cells in some cases can also home in on brain tumors being somehow attracted to them. This property has inspired researchers for years to consider using stem cells as a delivery mechanism to bring toxic agents right into the tumor, and a variety of clinical trials are ongoing in this area that in theory could be applicable to McCain.
Any such treatment would be highly experimental and have a high risk of failure and even potential harm. However, since most patients with glioblastoma die within about 1 year even with aggressive conventional treatments including surgery (McCain already had that when his tumor was discovered during blood clot removal), brain irradiation and chemo, risky interventions are quite justified.
What would stem cells deliver to the cancer in the way of a therapeutic punch to in theory more specifically work to help a brain tumor patient? A whopping 144 studies pop up on Clinicaltrials.gov for a search for “Glioblastoma” and “stem cells”.
Smart bombs. A number of these involve “loaded” stem cells carrying payloads to attack the tumor, which include a range of factors such as toxins and viruses. For instance, this cool Northwestern University trial mentioned in the Yahoo article cited near the beginning of this post uses viruses delivered by stem cells. Some of the stem cells used as smart bombs against brain cancer may be loaded with nanoparticles that they deliver to the tumor cells. Interestingly, whatever the “special delivery” of toxicity that the stem cells bring along, they can deliver it to the cancer cells in a variety of ways including via exosomes (little buds off of cell membranes containing small amounts of cellular material inside) or even fusing with the cancer cells to become one bigger cell containing the poison.
Immunotherapy. In a somewhat different approach, stem cells may also have a role to play in immunotherapy against brain tumors, an exciting area that is really taking off where the patient’s immune system is turbo-charged to specifically kill the tumor. The most talked about cancer immunotherapy today is called CAR-T, which is not technically a stem cell therapy but rather a “cell therapy”.
Protection of the good guys. Some of the trials take a different approach of using stem cells to hopefully benefit the patient by potentially protecting the normal cells in their brains from the harsh conventional treatments. In certain cases the stem cells have been genetically modified to be resistant to chemotherapy.
Overall, McCain has quite a battle in front of him with his glioblastoma whether he sticks to conventional therapies or goes into a clinical trial such as one using stem cells or some other new investigational therapy. I wish him the best.
The reason GM is so resistant to chemo or radiation because in the middle of tumor are in hypoxic environment and hibernating, not going through the cell cycle. When DNA splits, this is the time cancer cells are most sensitive to chemo and radiation. Stem cells are large in comparison with the size of micro vessels going to the center of the tumor and therefore it is not clear how the will deliver their payload, unless some cytokines or factors released by cells are active in tumor suppression.
Years back I conducted a study in GM patients using combination of perfluoro emulsion with chemo or radiation. Perfluoro emulsion particles are small (0.1-02 microns), can carry significant amount of oxygen through micro vessels to the hypoxic are of the tumor and push cancer cells to divide. This is when chemo or radiation is effective in killing cancer cells in hypoxic area. This is obviously not a cure but can prolong survival and what is most important, to improve patient condition. You can read my paper “Treatment of recurrent malignant glioma with BCNU-fluosol and oxygen inhalation. A phase I–II study”, Journal of Neuro-Oncology 32: 45–55, 1997.
John McCain is one of only a few leaders in fed government i would my children and grandchildren to emulate and I hope he can recover. But he will have financial help that most of us with terminal like ALS can only dream of