Treating glioblastoma multiforme (GBM) – the most common and aggressive form of brain cancer – is notoriously difficult. In the early 2000s, researchers began investigating a new form of therapy to attack GBM tumors: implanting stem cells engineered to express toxins that specifically kill tumor cells. The toxin – a protein called TRAIL – kills tumor cells (but not normal cells!) by signaling through a receptor that initiates cell death. Why use stem cells to express TRAIL? Stem cells have a handy tendency of migrating to sites of injury, including tumors. While promising in mice, this therapy has not been translated into human clinical trials for several reasons. A recent study addressed two prevailing problems:
Problem #1: about half of GBM tumors are actually resistant to being killed by TRAIL. To address this, the researchers identified a drug that sensitizes tumors to TRAIL by making the tumor cells localize the receptors to where it can actually sense TRAIL. Conveniently, this drug (cisplatin) is already a clinically approved chemotherapeutic drug.
Problem #2: GBM stem cell therapy has not been tested in a realistic scenario. GBM patients typically undergo surgery to remove tumors and chemotherapy after relapse. The researchers attempted to mirror this by surgically excising the GBM tumors and giving the mice cisplatin (chemotherapy) before starting treatment with TRAIL-stem cells. While this strategy certainly does not fully recapitulate GBM tumors in humans, it is a promising improvement.
Even with these problems addressed, there remain numerous obstacles to overcome before moving to the clinic. For example, do different tumors require different types of toxins? What are the most effective drugs to combine with stem cell therapy? Will implanting stem-cells produce any toxicity to surrounding healthy tissues?
There’s still a long road ahead, but studies like this are doing well to keep pushing forward.
Edited by Shay Neufeld. Many thanks to Harvard PhD students Katherine Rogers and Jonathan Henninger for providing expert opinion and insight on the article.
BBC news release ‘Cancer-killing stem cells engineered in lab‘
The original research paper
A comprehensive review of attempts to use stem-cell therapy for cancer treatment.