Strong Sleeping Pill
The new drug crosses the blood-brain barrier to kill glioblastoma cells. Photo: Pixabay

A research paper published in iScience speaks of a new anti-tumour drug that has shown the potential to destroy brain tumours, that too the most dangerous type of brain tumour. Scientists at the Gothenburg University are calling it Z4P which has successfully killed cancer cells in the brain. Previously, drugs couldn't cross the blood-brain barrier to destroy brain cells, a fact that protects neurons from invading foreign bodies. But Z4P has successfully breached that barrier.

The drug seems to work well with chemotherapy and has a long-lasting effect till six months, as shown in mouse models where Z4P killed all cancer cells in the brain but spared the healthy cells. The mice didn't relapse to cancer even after six months. Scientists have labelled this as "promising" stating that this new drug could be used in clinical practice in the next five years, especially for treating aggressive cancers.

These are the first clear results with brain tumours that can lead to a treatment which completely avoids surgery and radiation. We have also begun studying the use of our substance on other aggressive tumour forms like pancreatic cancer, triple-negative breast cancer and certain liver cancers.
Professor Leif Eriksson, Gothenburg University.

Why is this crucial?

As per the US National Brain Tumor Society, every year 10,000 or more people die of glioblastomas, a lethal type of brain tumour. Seven per cent of these people are only able to live for five years or more after they have been diagnosed with the disease. These mortality rates and survival rates have remained stagnant for many decades. As such a discovery like this could change the course of the disease.

How does it work?

The new wonder drug Z4P works by inhibiting the protein production of the brain tumour cells. These aggressive cancer cells usually act by hijacking the normal mechanism of cells and then use them to make the protein necessary for their own survival. So, when the drug blocks the stimulation of the pathway that creates the protein, the production stops. Without the proteins, the cancer cells are under stress which makes them commit suicide and die. In this way, Z4P destroys brain tumour cells.

We have now succeeded in stopping this hijacking by inserting a specially developed molecule in the cells that inhibits one of these hijacked adaptive mechanisms in the cancer cells. This causes the cancer to self-destruct.
Professor Leif Eriksson, Physical Chemistry, Gothenburg University.

Moreover, unlike other modes of brain tumour treatments, Z4P doesn't show any severe side effects. When the drug was tested in the animal models no change in their behaviour or weight was seen. The mice models didn't have any liver damage either, a critical side effect of such treatments. Further testing of cells treated with Z4P revealed no toxic elements even at high doses, so the drug is presumably non-toxic.

How will it change cancer therapy?

Most cancer treatment relies on chemotherapy or surgery which isn't 100% on target and often leaves some cancer cells in the body. It also kills some healthy cells in the process. But with this drug, we can specifically target the cancer cells and there's little to no chance of relapse as all cancer cells could be killed.

Today, cancer treatment consists of surgery, radiation and chemotherapy. Unfortunately, all cancer cells are not killed and the tumour returns. Once the cancer relapse, the tumour cells have often spread and developed resistance.
Professor Leif Eriksson, Physical Chemistry, Gothenburg University.

Previously, doing such targeted drug therapy in the brain wasn't possible as no drug could evade the blood-brain barrier. The scientists used computer simulations to make a refined form of Z4P which could invade the blood-brain barrier effectively.

With all the obstacles gone, this could become an effective way of treating cancer without using chemotherapy or radiation and without undergoing surgery.

Can it treat all types of cancers?

However, this specific drug therapy can't be used for all types of cancer. It's not even applicable to all types of brain tumours. Since it targets a particular pathway involved in a particular type of brain tumour, namely, glioblastoma, it is only applicable to those.

The next steps

It largely depends on whether funding comes in that allows taking the different steps as smoothly as possible. If I'm optimistic, perhaps it might take five years. That's a short timeframe, but at the same time glioblastomas are nearly 100 per cent fatal, so any improvement in medical care is major progress.
Professor Leif Eriksson, Physical Chemistry, Gothenburg University.

Based on the results, the scientists are going forward with the next stage of animal experiments by optimising the experiment according to the new animal models.

Although the studies are still underway, scientists are certain that this promising drug will soon enter the medical treatment pipeline.

However, developing such a drug is a long tedious process involving various levels of animal model lab studies which are called preclinical studies. After this hurdle, the drugs enter the investigative stage where applications are sent to FDA for clinical trials. Once approved they have to undergo Phase I, II and III trials in humans where the effectiveness and efficiency of the drug are tested.

After a positive result in the trials, a new drug application is made to the FDA giving all the details of the drug. If FDA finds the application up to the standards it approves the drug after a thorough review of its manufacturing, processing and packaging techniques, and then it can enter the medical treatment pipeline. However post-marketing surveillance is done at this stage to determine any side effects of the approved drug, and if found the drug could be removed from the market.

Only 1 out of 10000 drugs make it through the entire process and enter the market.