2 min readResearchers Take Key Step Toward Cancer Treatments that Leave Healthy Cells Unharmed

Corvallis, OR — Researchers have opened up a possible avenue for new cancer therapies that don’t have the side effects that oftentimes accompany many current cancer treatments by identifying a protein modification that specifically supports proliferation and survival of tumour cells.

Depending on the kind of cancer and the type of treatment, a patient might suffer from many side effects, including anemia, loss of appetite, bleeding, bruising, constipation, delirium, diarrhea, fatigue, hair loss, nausea, sexual issues or bladder problems.

Scientists at Oregon State University, the University of Central Florida and New York University made the protein-modification discovery while studying neurofibromatosis type 2. The condition, commonly known as NF2, is characterized by the development of tumors of the nervous system called schwannomas.

“The hallmark of tumour cell behaviour is their uncontrolled growth,” said Maca Franco, professor of biochemistry and biophysics in OSU’s College of Science. “Tumors cells need to constantly produce energy and building blocks to replicate.”

Researchers led by Franco and Oregon State undergraduate student Jeanine Pestoni found that schwannoma cells produce an oxidant and nitrating agent, peroxynitrite, which modifies an amino acid, tyrosine, in proteins.

When tyrosine becomes nitrated in specific proteins, an effect is the reprogramming of the tumour cells’ metabolism, enabling them to proliferate.

“To sustain persistent growth, tumour cells change the way they produce energy and building blocks and present a signature metabolic phenotype that differs from that of normal cells,” Franco said. “We discovered that peroxynitrite, the most powerful oxidant produced by cells, controls the metabolic changes that occur in tumour cells of the nervous system and supports their growth. We believe that there are specific proteins that when they become nitrated acquire a new function they did not have before, and this new function may control tumour growth.”

Peroxynitrite is produced at high levels in “pathological conditions,” she said – such as those found in tumors – but not in normal tissues. 

“This opens up the exciting possibility of targeting peroxynitrite production exclusively in tumour cells as a new therapeutic strategy for the treatment of tumours of the nervous system, with minimal to no side effects on normal tissues,” Franco added. “We are uncovering a completely new category of targets for the treatment of solid tumours, and not only tumours of the nervous system – it may have broader implications for the treatment of several cancer types. We can go after proteins that usually aren’t modified in normal cells; we can target those modified proteins with inhibitors that don’t affect normal cells, hopefully developing a treatment with minimal side effects.”

Article adapted from a Oregon State University news release.

Publication: Peroxynitrite supports a metabolic reprogramming in merlin-deficient Schwann cells and promotes cell survival. Pestoni, JC et al. Journal of Biological Chemistry (July 26, 2019): Click here to view.

Cancer Therapy, neurofibromatosis type 2, NF2, peroxynitrite, schwannomas, Tumour

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