Glioblastoma: killing brain tumor cells

As stated previously, I usually don’t write about experimental research unless there is a good reason to do so. Preliminary findings have a way of changing. That’s why they are preliminary.

However, glioblastoma is a common form of brain tumor, and the five-year survival rate is a pathetic 5%. Further we have a class of experimental drugs, one of the most promising of which is designated KL-50, that may be in clinical trials in the relatively near future and that preliminary testing has shown to be quite effective against this horrible disease.

This new class of drugs is a direct attack on the disease. They cause fatal damage to the DNA of cancer cells without harming non-cancerous cells in the body.

Cancer cells are simply normal cells that have incurred mutations causing uncontrolled growth. There are a variety of factors that can cause these mutations, including chemicals, radiation and types of air and water pollution.

Treatments for cancers in the past have included:

• Surgical removal of cancer cells
• Chemo and radiation therapy
• Immunotherapy

The first two present substantial risks either for missing cancer cells or for inflicting damage on healthy cells. Where the brain is involved, that can mean physical or cognitive impairment — a risk that cannot be taken lightly.

The effectiveness of immunotherapy depends on the state of the patient’s immune system. In a younger and otherwise healthy individual, this can be extremely effective. Conversely, for someone with a depressed immune system, it simply may not work. As discussed in a prior post, the immune system does deteriorate with age.

The new class of drugs directly attacks the DNA strands in cancer cells, inflicting fatal changes on those strands.

DNA damage can occur in normal cell reproduction, and cells have a couple of methods or pathways for correcting errors in DNA replication.

• The first involves a protein, O6-methylguanine methyl transferase (MGMT). However, glioblastoma cells have been found to be deficient in this protein.
• The second is the DNA mismatch repair pathway. This is a process in which replicates of a DNA strand are checked against the parent strand for inconsistencies. If an error is found, that portion of the strand is replaced.

The new class of drugs operates on strands that are deficient in MGMT and in such a way that the mismatch repair pathway cannot correct the damage. Healthy cells have MGMT are so are untouched. Cancer cells deficient in MGMT die.

The new class of drugs for glioblastoma appear to be in Phase 2 of the FDA’s development and approval process.(2) That’s the phase in which the drugs are tested in animals, for example, mice that have been implanted with human brain cells.

Phase 3 will involved clinical trials with human subjects. Patients with glioblastoma may want to search for a trial in which to participate. While clinical trials always involve some inherent risk, the poor survival rate with glioblastoma means that there is really minimal downside in participation.

The NIH Library of Medicine runs a global database of clinical trials which can be sorted by disease as well as whether the trial is actively recruiting participants. The link for this database is shown in the notes below.(3) In the US alone, there are 193 clinical trials for glioblastoma that are actively recruiting and 26 that have not yet started to recruit.

This new class of medications may also suggest new ways to attack other cancers. That’s a more distant prospect, but we can hope.

Sources:

1. https://www.nih.gov/news-events/nih-research-matters/customized-drug-kill-brain-cancer-cells
2. https://www.fda.gov/drugs/cder-small-business-industry-assistance-sbia/new-drug-development-and-review-process
3. https://clinicaltrials.gov/

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