What is Cancer - A Failure of Apoptosis (How Cancer Develops)
A Failure of Death...but What IS Cancer?
The average adult human body creates around 60 billion new cells each day by somatic cell division (mitosis). Therefore, an equal number must also die to maintain the cell number - this is known as cell homeostasis. There are several ways a cell can die (each will be explained in depth in an upcoming hub):
- Necrosis: Uncontrolled cell death. Basically, the cells burst, spewing their contents into the surrounding tissue fluid. This causes inflammation, pain and swelling. Necrosis is usually the result of cellular injury or infection.
- Apoptosis (Programmed Cell Death 1): Apoptosis is a tightly regulated, multi-step pathway responsible for cell death during development and tissue homeostasis. Enzyme action is required for this (unlike necrosis) - Genetic control is maintained right to the end.
- Programmed Cell Death (Non-Apoptotic): Cell death is still controlled, but lacks some of the key characteristics of Apoptosis. Protein synthesis and genetic activity seen until the cell is engulfed.
Disruption of the cell division-cell death balance can be catastrophic. Where Mitosis outstrips Apoptosis, cancer can develop; Apoptosis outstripping Mitosis can lead to degenerative diseases such as certain forms of Dementia
Apoptosis - Our Defence against Cancer
Apoptosis is the major mechanism by which misplace, unnecessary or irreparably damaged cells are removed from the organism. As such, cellular escape from apoptosis is a critical requirement for tumorigenesis. As can be seen from the diagram "Acquired Capabilities of Cancer" below, tumorigenesis is a multi-step process.
When does a Tumour become Cancer?
Cancer cells are cells that have become immortal. They have escaped the Hayflick limit, which states that a single normal body cell can only divide between 40 and 60 times before being permanently destroyed. A single immortal cell does not a cancer make, however: the acquisition of the 'tissue invasion' trait that marks out a cell as an invasive, malignant cancer
It can be argued that tumour development is a process similar to that of Darwinian evolution. The cancer cells undergo a series of genetic changes. If this change confers a type of growth advantage over the surrounding cells (a favourable process in evolution, not so favourable in a multi-cellular organism where the cells are supposed to be working in perfect synchrony), then the cell has taken another step towards become cancerous.
It must be noted that cancer cells require several new traits in order to survive. Without sustained angiogenesis (blood vessel formation), self sufficiency in growth signals (because they are not coming from the body), and insensitivity to anti-growth signals (which WILL be coming from the body in an effort to quell this uprising), the 'proto-cancer' cells can still die by other means, even if they have escaped Apoptotic Programmed Cell Death
The Acquired Capabilities of Cancer
All Cancers are not Created Equal
The order in which a cell attains the different of capabilities typical of a cancer phenotype can differ, as highlighted in the two six step pathways. The number of mutations required for a cancer phenotype can also differ. In some tumours, a particular genetic mutation may confer several capabilities simultaneously: the five step pathway illustrates a loss of function mutation in p53, which confers both resistance to apoptosis and sustained angiogenesis. In other tumours, it may take several mutations to acquire a certain capability: the eight step pathway requires two steps to acquire tissue invasion/metastasis and evasion of apoptosis.
It is easy to think that once a tumour has developed, all apoptotic mechanisms have been shut off in the vicinity. As proven by Kerr, Wyllie and Currie (1972), the observed growth rate of tumours is lower than it should be. This is due to a surprisingly high level of endogenous tumour cell apoptosis. The uncontrolled proliferation of cells that is characteristic of cancer can be due to:
- Increased Mitosis
- Decreased Apoptosis
- A combination of the two
Indeed, the defensive apoptotic machinery is usually intact in cancer cells (with the exception of one or two key bcl-2 or p53 mutations- but its activation threshold is much higher. Due to this, reactivating apoptosis in tumour cells is a tangible possibility.
How is Cancer Treated?
By now you should have a more in depth knowledge of the molecular causes of cancer. It is this understanding of how cancer develops, proliferates, and survives where it shouldn't, that has allowed ever-more effective therapies to be developed. In the war against cancer, knowledge is our greatest weapon. Part three of this mini series will look at cancer therapies, and how they work
Where Next? Cancer
- Cell - Hallmarks of Cancer: The Next Generation
A beautifully descriptive review paper published in the Journal Cell. Please give it a look over, if for nothing else other than the diagrams. Extremely informative. You can download a PDF version of the paper for free.
- What Is Cancer? - National Cancer Institute
Definition of cancer, a brief explanation of the origins of cancer in cells, basic cancer statistics, and links to other NCI cancer-related resources.
- Milestone 1 : Nature Milestones in Cancer
An excellent review by the Journal 'Nature' into the milestones in cancer research. Number 12 discussed Kerr, Wyllie and Currie's 1972 paper