Noun:
1. The study and treatment of tumours, including the origin, development, diagnosis, and treatment of malignant neoplasms. Comes from the Greek 'ónkos', meaning 'mass' or 'lump'.
I hadn't realised it yet, but before attending the Oncology course at the UNIQ summer school at the University of Oxford, I didn't actually know a great deal about cancer. Infact, I thought that the brief description of cancer in my AS biology textbook was quite an accurate explanation of the disease. However, after my very first lecture, it soon became clear to me that 'a mass of cells undergoing uncontrolled and rapid mitosis' was an explanation that merely scratched the surface of the true nature of a malignant tumour.
Saying that the cells in a tumour are undergoing uncontrolled hyperplasia is not an incorrect statement; it's true that this feature is observable in all tumours. It is, however, merely a characteristic, not a definition. In 2000, cancer researchers Douglas Hanahan and Robert Weinberg published an article in the scientific journal Cell entitled 'The Hallmarks of Cancer'. This comprised of six features which characterised the disease on a biological level, establishing it as a heterogeneous and incredibly variable condition. In 2006, this list was revised and four more characteristics were added. The ten hallmarks give us a valuable insight into the sheer complexity of the disease, a complexity that stretches far beyond the popular idea that cancer is a lump of identical cells. They represent a group of molecular, biochemical, and cellular traits shared by most cancers, which are both key concepts to understand when developing drugs and treatments against cancer, and also important characteristics to look out for when diagnosing a patient with cancer.
Before going into the hallmarks themselves (I will do this in my next post), it is important to understand that a tumour is not just a group of identical epithelial cells. The theories of natural selection and evolution apply just as much to the cells within a tumour as they do to animals and plants in the environment. When a protein in a cell acquires a mutation, it may develop a competitive advantage over the surrounding cells, and the environment in which it lives may be favourable to that mutated protein. Diversity between cells breeds success and this cell with the advantageous characteristic may go on to survive and reproduce, passing on the characteristic to the offspring. Over time, and after many random mutations have been acquired, the tumour is composed of many different populations of cells, each one different from the adjacent cell. The tumour becomes a family tree of slightly different cells which may be unrecognisable from the original cell, and this means that a doctor, when treating a cancer patient, may in essence be dealing with 17 different diseases. This is why early diagnosis is key, and also why a combination of treatments (for example combining chemotherapy and radiotherapy) may be the most feasible option. Another point to consider is that the molecular signature of each patient's tumour is different: mutations occur randomly so it is impossible to generalise a treatment and assume that what is effective for one individual is effective for everyone else.
Proteins within a cell exist in networks of communication. The 'mechanics of life' depend on the metabolic pathways within a cell, and the inter- and intracellular communication and teamwork that exists there. Proteins fire signals and commands between eachother to regulate the cycle of the cell, stimulating each protein to do it's particular job. This biological machinery is responsible for regulating a cell's proliferation, differentiation and death, and when a mutation occurs in one of the proteins in the pathway major problems can be caused in terms of the genes and characterises expressed. Many genes are responsible for telling the body what proteins to make, and in what quantity. Mutations present in the genes of cancer cells may prevent them from regulating normal cell proliferation for example, giving rise to one of the biological hallmarks: enabling replicative immortality.
Cancers speed their growth by accumulating mutations in genes which normally fix DNA damage. By disabling cellular repair systems, mutations can be preserved. This promotes the accumulation of more faulty genes within cells which ultimately fuels the evolution of the cancer. Acquiring a mutation which causes a gene that should be expressed to be suppressed (or vice versa) can affect the physiological smooth-running of the cell and the communication within the protein network, ultimately dictating its malignant growth.
There are two main types of genes that play a role in cancer development: oncogenes and tumour suppressor genes. Proto-oncogenes are genes which usually control when and how much the cell divides: they encode for proteins which stimulate cell proliferation, inhibit cell differentiation and halt cell death. When a proto-oncogene develops a mutation however (it is now called an oncogene) these proteins are over-expressed and malignant growth is stimulated. This is ultimately why cancer is such a successful disease: it exploits the very features that make the human body so efficient.
Tumour suppressor genes are normal genes which control and slow the rate of cell division, and can be thought of as a set of biological brakes in a cell. If these types of genes develop mutations, the proteins responsible for controlling mitosis are suppressed, giving rise to another important hallmark of cancer: evading growth suppressors. In summary, the difference between an oncogene and a tumour suppressor is that malignancy of cells can result from the 'turning on' of proto-oncogenes (to become dangerous oncogenes) but the 'turning off' of the tumour suppressor genes.
In my next blog post I will be going through each of the hallmarks of cancer, explaining the physiological processes involved and why each specific trait poses such a problem to the biological machinery of the body.
Thankyou for reading!
Francesca
Sources:
http://www.cancer.org/acs/groups/cid/documents/webcontent/002550-pdf.pdf
http://www.nature.com/scitable/topicpage/proto-oncogenes-to-oncogenes-to-cancer-883
http://en.wikipedia.org/wiki/The_Hallmarks_of_Cancer
http://www.cell.com/cell/abstract/S0092-8674(11)00127-9
http://evolutionary-research.net/science/intro/the-engine-of-evolution/mutations-in-proteins-genes-genomes
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