A new study published in the Journal of Biological Chemistry, has identifying a protein modification that specifically supports proliferation and survival of tumour cells.
Scientists have found 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 anaemia, loss of appetite, bleeding, bruising, constipation, delirium, diarrhoea, fatigue, hair loss, nausea, sexual issues or bladder problems.
The findings were published in the Journal of Biological Chemistry. Scientists made a protein-modification discovery while studying neurofibromatosis type 2. The condition, commonly known as NF2, is characterized by the development of tumours of the nervous system called schwannomas.
“The hallmark of tumour cell behaviour is their uncontrolled growth. Tumours cells need to constantly produce energy and building blocks to replicate,” said Maca Franco, professor of biochemistry and biophysics.
Researchers 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,” said Franco.
She further added, “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 tumours – 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.
She continued, “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 treatment with minimal side effects.
