Autism spectrum disorder (ASD) is a developmental disability that can cause significant social, communication and behavioral challenges.

There is often nothing about how people with ASD look that sets them apart from other people, but those with ASD may communicate, interact, behave and learn in different ways than most other people. About 1 in 68 children has been identified with ASD, according to estimates from CDC's Autism and Developmental Disabilities Monitoring (ADDM) Network.

Recent research has used ASD to look at devastating diseases such as brain cancer. Glioblastomas (GBMs) are tumors that arise from astrocytes — the star-shaped cells that make up the supportive tissue of the brain. These tumors, the most common and aggressive form of brain cancer, are usually highly malignant because the cells reproduce quickly, and they are supported by a large network of blood vessels.

GBMs are generally found in the cerebral hemispheres of the brain but can be found anywhere in the brain or spinal cord. GBMs increase in frequency with age and affect more men than women.

So, exactly what is ASD teaching us about brain cancer?

Researchers at The Johns Hopkins University have discovered why elevated levels of the protein NHE9 add to the lethality of GBMs. Their discovery suggests that drugs designed to target NHE9 could help to successfully fight the deadly disease.

Rajini Rao, Ph.D., a professor of physiology at the Johns Hopkins University School of Medicine, claims that research on cargo transport inside the cells of patients with autism has led to a new strategy for treating a deadly brain cancer.

All animal and human cells contain many "cargo packages" surrounded by membranes. These so-called endosomes carry newly minted proteins to specific destinations throughout the cell and haul away old proteins for destruction.

Their "shipping speed," or level of acidity inside the endosomes, is controlled by balancing the activity of protein "pumps" that push protons into endosomes to increase their acidity with that of protein "leaks," like NHE9, that remove protons.

Rao's research group previously showed that autism-associated defects in the protein NHE9 are harmful because they "clog the leaks," leaving endosomes too acidic and making them race to remove cargo from the cell membrane, which prematurely destroys proteins.

To better understand NHE9, graduate students and postdoctoral fellows in Rao's lab searched through patient databases to see if it had other effects on human health. They found that elevated levels of NHE9 are associated with resistance to radiation, chemotherapy and poorer prognoses for patients with GBMs.

Together with Alfredo Quinones-Hinojosa, M.D., a professor of neurosurgery at Johns Hopkins, the researchers examined NHE9 in tumor cells from several patients. They found that cells with low levels of NHE9 grew the slowest, and those with the highest levels grew fastest.

Similarly, the cells with the most NHE9 traveled fastest when placed on a surface similar to that of the brain, suggesting a high potential for metastasis. This was confirmed when the tumor cells, which were manipulated to have high or low NHE9, were transplanted into the brains of mice.

Using knowledge gained from their autism research, the team suspected that the boost NHE9 gave to GBMs was explained by abnormal endosome acidity. Further studies revealed that, in contrast to autism, NHE9 is overactive in brain cancer, causing endosomes to leak too many protons and become too alkaline. This slows down the "shipping rate" of cancer-promoting cargo and leaves them on the cell surface for too long.

One such cargo protein is EGFR, which maintains cancer-promoting signals at the cell surface and helps tumors become more robust so they grow and move faster. EGFR is also found at elevated levels in more than one-half of patients with glioblastomas. Drugs targeting EGFR in these patients are sometimes effective.

The team discovered that alkaline endosomes slow down the removal of EGFR from cell surfaces. Lab-grown tumor cells were more readily killed when treated with both a drug countering NHE proteins and a drug against EGFR than when treated by the EGFR-targeting drug alone.

Autism can teach us a lot about brain cancer. Although this idea has not yet been tested in patients, the results of this research team are encouraging, hopefully making brain cancer less aggressive and devastating.