Overactive Marker May Shorten Survival of Brain Tumor Patients

Researchers may have discovered a more accurate way to predict how long patients with the deadliest form of brain cancer will live, according to an analysis by researchers from the University of Alabama at Birmingham (UAB) published today in the journal PLOS ONE. The authors say the finding could better inform physician recommendations on the most appropriate treatment strategy for patients with aggressive brain tumors.

The new analysis examined tumors from patients with glioblastoma multiforme (GBM), who survive 12-15 months on average with the current combination of surgery, radiation and the chemotherapy temozolomide. GBM’s deadliness is due not only to its staggering growth rate and location in the brain, but also to how quickly GBM cells become impervious to treatment.

While radiation and temozolomide usually kill most GBM cells, those that survive can quickly multiply to fill the void. Tough, treatment-resistant tumor cells soon comprise most of the recurring tumor, and 90 percent of recurring tumors show no response to temozolomide. At this point, patients have few options, most of which merely bring comfort before death.

Into this grim picture comes the current study result, which found that the 25 to 30 percent of GBM patients whose tumor cells have an overactive version of the enzyme cytochrome c oxidase (CcO) live less than half as long as patients with a less active version.

“Our study reports for the first time the role of cytochrome c oxidase as a prognostic marker in GBM patients’ tumor tissues,” said Corinne Griguer, Ph.D., associate professor in the Division of Neurosurgery within the UAB School of Medicine and study leader. “High CcO activity comes with a 25-fold increase in risk of death.”

Presently, all patients with GBM tumors are lumped together in various prognostic models. The current study found, however, that patients with highly active CcO lived six months on average, whereas those whose tumors had lower CcO activity, closer to levels in normal tissues, lived 14 months.

The team investigated the relation between tumor CcO activity and survival times of 84 patients diagnosed with primary GBM and treated at UAB. They found that patient survival time tracked closely with CcO enzymatic activity, and without regard to subsequent therapies. Analysis of tumor tissue from a second group of European GBM patients yielded nearly identical results.

Types of brain tumours

There are many different types of brain tumours. And each of those can come in faster growing or more slowly growing forms. So there is no single situation we can describe here.

Some people have slowly growing brain tumours that cannot be cured. But with a very slow growing tumour, you may live for many years before the tumour causes any serious effects. Depending on your age when you are diagnosed, the tumour may eventually cause your death. Or you may live a full life and die from something else. It depends on the type of tumour, where it is in the brain and how well it responds to treatment.

Other people have fast growing tumours that may respond well to treatment, but then come back.

Sometimes brain tumours are diagnosed at an advanced stage. The tumour may be too advanced to be cured with treatment. But treatment may shrink the tumour, and so slow down its progress.

In some situations, your specialist may think that a long course of radiotherapy or major surgery may not help you, or may even make matters worse. If this is the case, your specialist will talk this through with you. Depending on the type of brain tumour you have, if you are too ill to be up and about and looking after yourself when you are diagnosed, you are less likely to be helped by intensive radiotherapy. It may even increase your problems so that you can do less for yourself after the treatment than before.

Similarly, with surgery, you have to be fit enough to be able to make a good recovery from your operation. The more ill you are, the more likely you are to spend longer in hospital getting over your treatment. If your specialist suggests that intensive treatment may not help you, it is because your specialist wants to help you to make the most of the time you have. And they may be reluctant to give you treatment that overall may make matters worse for you and your family.

Of course you can still have other treatment to help to control your symptoms and keep you as well as possible for as long as possible. A shorter course of radiotherapy may slow down or even shrink your tumour, helping you to feel better for longer.

Why CcO?
Most studies on CcO to date have focused on its role in a chain reaction in which the mitochondria, the powerhouses of human cells, produce energy. CcO, with the help of oxygen, turns sugar from food into energy needed for survival in a series of chemical reactions that use a process called oxidative phosphorylation (OxPhos). Energy mechanisms become relevant because of how cancer cells use energy as they seek to survive and resist therapy.

Different types of brain tumour

There are many types of benign brain tumours and primary malignant brain tumours. Many are very rare. The following is a brief description of the most common types.

Meningiomas are usually benign. They grow from cells in the meninges (the tissues that surround the brain).

These are high-grade malignant tumours that grow in the cerebellum. They are uncommon in adults, but are one of the two most common brain tumours in children. The other is astrocytoma in the cerebellum.

These are malignant primary brain tumours that arise from glial cells. There are various types, depending on the cell of origin - for example:

  Astrocytomas (originating from astrocyte cells.) There are various types of astrocytoma. They include:
      Low-grade astrocytomas.
      Anaplastic astrocytoma. This is a high-grade tumour.
      Glioblastoma multiforme. This is a high-grade tumour which tends to grow quite quickly. It is the most common type of primary malignant brain tumour in adults.
  Oligodendrogliomas (originating from oligodendrocytes). These can vary in their grade.
  Ependymoma (originating from ependymal cells). These are rare, but are usually low-grade.

Primitive neuroectodermal tumours (PNETs)

These are very similar to medulloblastomas and mainly occur in children.
Pituitary tumours

There are various types of tumour which arise from the different cells in the pituitary gland. They tend to be benign. However, the cells of the tumour may produce large quantities of hormones which can cause various symptoms. As they grow, they may also cause pressure symptoms. The optic nerves (the nerves of sight) are near to the pituitary and so a growing pituitary gland tumour may press on an optic nerve and affect vision.
Acoustic neuroma (schwannoma)

This is a benign tumour which arises from Schwann cells which cover the nerve that goes to the ear. Symptoms can include deafness on the affected side and vertigo.

There are various other rare types of benign and primary malignant brain tumours.

The current study is among the first to examine the role of CcO in mechanisms that determine how cancer cells use energy. The team found that cancer cells with higher CcO activity generate more energy and are better able to survive chemotherapy.

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