3: What is cancer,
what is a brain tumour
and what does it do?
Brain tumour is a form of cancer, cancer patients are treated by oncologists, but brain tumours, because of their location, involve issues distinct from other forms of cancer. Neuro-oncologists specialise in brain tumour. There are few specialist neuro-oncologists in Australia. They have a huge role in advising general oncologists for whom brain tumours are a small percentage of case load.
There is a paper on cancer in Australia 2006 published by the Australian Institute of Health and Welfare on the web — of research more than immediate practical interest, click here to download. It requires Adobe Acrobat Reader, obtainable free here.
The sad thing is that medical science still does not know what causes cancer, that is, why cells turn tumorous. There are several distinguishing features of tumour cells, but exactly why and in what order cells change to be like this is not settled. Some key factors are:
1. cells alter the way in which they make energy, they alter their respiration. In healthy organisms, including people, mitochondria in every cell make an abundance of energy and also carbon dioxide from sugar and oxygen. Tumour cells abandon this and make energy from sugar alone in the manner of bacteria, or of all cells before the appearance of mitochondria a billion and a half years ago, so there is something retrograde happening in the cell.
2. cells undergo mutation, and this mutating process can increase in pace and be very diverse. This is the quality which is most evident as tumours grow and spread. Particularly because of the attention in biology to the human genome, gene issues tend to be the focus of research, though whether the mutation precedes the altered respiration seems not settled, and thus whether gene research will solve the What-Causes-Cancer question is moot.
3. cells 'differentiate', 'de-differentiate' and 're-differentiate'. That's how we got to grow from a single cell, it's also part of the mystery of wound repair. Look at a scratch and marvel at the process whereby appropriate cells get whacked into place in wound repair. Were they different local cells that de-differentiated and then re-differentiated into the required type? Or did signals go out around the body for the right type? We do that stuff all the time, amazing. BUT: cancer cells lose the ability to 'differentiate'.. they become self-driven rogues. People generally have some cells making mistakes, pursuing aberrant growth and reproduction patterns, all the time — in the late 1960s, a study of bodies of healthy car accident victims in the United States found 'cancer' in every person over fifty. There are natural regulatory systems which normally allow us to avoid progressive disease by eliminating such problem cells. The mitochondria in healthy cells appear to keep watch and cause a deranged cell to commit a kind of euthanasia, known as apoptosis, if they are coping with life. Some theories of cancer think in terms of one rogue, mutated cell leading on to millions. On the other hand, given that the mechanism of tumorigenesis (a healthy cell becoming a cancer/tumour cell) is not understood, doctors also recognise that there may be an ongoing process of tumorigenesis - no matter how many tumour cells you kill with treatments, somehow more cells are going the same way.
4. tumour cells can - in malignant and aggressive forms - reproduce very rapidly. In medicine various things are graded from I to IV (1 to 4) in order of severity. Tumours are graded I to IV according to degree of malignancy and aggressiveness ('benign' growths are not graded). The pathology of tumours is not simple and even the best institutions do not always agree on the identity and grading of tumour samples. More skill is coming, including genetic differentiation which, while not providing a cure in brain tumour, may assist in identifying for whom a given treatment may be suitable.
5. there is another important piece of information. Tumour cells, as they proliferate, need a lot of blood supply to feed them. They thus develop new blood vessel systems which are messy and very different from normal healthy blood vessel systems. This creation of new blood vessels is called angiogenesis and opens the door to some treatments which try to stop angiogenesis - anti-angiogenesis.
Brain tumours have some distinguishing characteristics:
1. they develop in a very confined space. This means that their major damaging role is 'mass effect', taking space themselves and also causing inflammation and swelling of other cells.
2. operating on the brain is difficult and fraught with risk of complication. Tumours may be in locations of the brain so critical to life that they are deemed 'inoperable'.
3. there is a blood-brain barrier which means that the world inside the brain is different and transfer of materials between the brain and the rest of the body is limited.
4. some tumour cells from other parts of the body enter the brain and produce brain metastases [colloquially 'mets'] — tumours in a new part of the body are called metastasis. Tumour cells in places copiously supplied with blood (the lung is a striking example) or in cells of a type which have properties of mobility (e.g. melanoma, in melanocytes) can migrate more easily than some others; but there is less prospect of tumour cells leaving the brain — though in part this may be because aggressive malignant brain tumours can kill with such speed that migration elsewhere is not an issue. As treatment prospects improve, as more treatments — notably more operations — occur, and survival times increase, metastases outside the brain might arise.
5. it was believed that the blood-brain barrier prevented most chemotherapy drugs from reaching the brain... until it was realised a few years ago that drugs taken often by brain tumour patients, particularly anti-inflammatory and anti-seizure drugs, can alter bodily metabolism such that many chemotherapy drugs are broken down before having a chance to act... So many earlier brain tumour trials of standard chemotherapy drugs are needing to be redone. It may be that radiotherapy may open up the blood-brain barrier for a short time after RT is concluded, thus allowing chemotherapy drugs to take effect.
6. there is one chemotherapy drug, temozolomide (TMZ, Temodal), which succeeds in getting more effectively to brain tumours and which has fewer side effects. This became available in Australia for use monthly under the Pharmaceutical Benefits Scheme (PBS) in 2000. In 2006 it became available on a new basis, as an adjunct to radiotherapy. It is, as with other treatments, effective only for a portion of the patient population.