Tumor-killing Virus Nearly Doubles Survival Time of Brain Cancer Patients

To defeat the deadliest of cancers, it’s time to unleash the viruses.

In a small clinical trial with brain cancer patients, a tumor-seeking virus successfully invaded cancer cells and smuggled in molecular detonators, allowing doctors to selectively blast the deadly growths with a toxic drug. In the trial’s 45 participants, who were fighting the most aggressive forms of brain cancer known, the virus-drug combo nearly doubled their average survival time while showing no dangerous side effects. The finding, published Wednesday in the journal Science Translational Medicine, demonstrates the utility of such viruses and also provides a green light for the treatment strategy to move on to more trials.

Source: Tumor-killing virus nearly doubles survival time of brain cancer patients

Paging Gord Downie.

Ultrasound Helps Drugs Sneak Past the Blood-Brain Barrier

Here in the S-wing of Toronto’s Sunnybrook Hospital, Mainprize and his research team accomplished on Thursday what no one in the world has ever done before: Using focused ultrasound waves, they have opened the human blood-brain barrier, paving the way for future treatment of an array of currently impossible or hard-to cure-illnesses – from brain cancer to certain forms of depression, stroke, Parkinson’s disease and Alzheimer’s disease.

Source: Sunnybrook doctor first to perform blood-brain barrier procedure using focused ultrasound waves

I’m not very keen on intentionally tearing even small holes in capillaries. It may work well for tumors, since the goal is to damage that tissue anyway. But using this to deliver drugs to healthy tissue sounds problematic. The Blood-Brain Barrier exists for some very good reasons. If used in healthy tissue this would essentially imitate a small hemorrhagic stroke for 8-12 hours. That’s a lot of time for glutamate toxicity alone, and there are many other substances in systemic circulation that aren’t tolerated well in the brain.

Antidepressants Plus Blood Thinners Cause Brain Cancer Cells to Eat Themselves in Mice

In a study appearing in Cancer Cell on September 24, Swiss researchers find that antidepressants work against brain cancer by excessively increasing tumor autophagy (a process that causes the Cancer Cells to eat themselves). The scientists next combined the antidepressants with blood thinners—also known to increase autophagy—as a treatment for mice with the first stages of human glioblastoma. Mouse lifespan doubled with the drug combination therapy, while either drug alone had no effect.

…”Importantly, the combination therapy did not cure the mice; rather, it delayed disease progression and modestly extended their lifespan,” Hanahan says.

Source: Antidepressants plus blood thinners cause brain cancer cells to eat themselves in mice

It won’t work against every brain cancer, some will also resist that particular signal to initiate apoptosis. It might not work in humans, mice are still a biological model not a human. It’ll take a decade or two to get through all the human trials and safety requirements.

I had to read the article to find out the blood thinner used was: ticlopidine (AKA Ticlid).  Ticlid was taken off the US market.  The article mentions that Plavix works in it’s place.  The tricyclic antidepressants used were desipramine (DMI) and trifluoperazine (TFP).  Optimistically, it won’t take long for this combination to gain traction – ~5 years I’d guess, and lots of people will benefit from stage 2/3 trials in the mean time. Approval for drugs which already have a proven safety profile is much much faster than for other drugs, many of which only take the 2 decades you list from discovery or synthesis to reach that point.

What leads to scientists deciding to test two drugs for totally unrelated conditions on a third unrelated condition?

There is a lot of background/buildup work for something like this to be discovered.

In this case, someone tested antidepressants on cancer cells and found an increase in the rate of auto-destruction. Then, somewhere else another person tested blood thinners on cancer cells and observed the same thing.

These studies would have identified why this is happening, via two different biological mechanisms, and published that information. Then this third group would have read both studies, seen that they accomplish autophagy in different ways, and thought: “Maybe if we try both route A and route B to destroy the cells, it will destroy it twice as fast.”

It’s just educated guessing.

How do you give a mouse brain cancer?

Because the mice they use are inbred mouse lines, they’re all essentially clones of each other. This also happens to mean you can transfer cancer cells from one into another without rejection occurring. The cancer will then progress normally in the recipient mice. I can’t see the paper (this article came out ahead of print), but it’s likely they transferred glioblastoma cells between mice.

Similarly, you can use SCID (Severe Combined ImmunoDeficiency) mice, which have their immune systems completely knocked out.  You can do a xenograft, where you take a glioblastoma cell line from any species, and implant it into the mice. The cancer would then spread normally.

How Brain Tumours Adapt Through Complex Ecosystems

Despite advances in medical technology and a constantly evolving understanding of the mechanisms of cancer progression, researchers and clinicians are faced with a litany of challenges along the road to finding a cure for the most aggressive forms of cancer. This is particularly true of glioblastoma multiforme, the most common and most aggressive form of human brain cancer.

Source: Survival of the fittest: how brain tumours adapt through complex ecosystems