David J. Argyle, BVMS, PhD, DECVIM-CA (Oncology), MRCVS
Cancer is a disease of all vertebrate species and is well documented throughout history, with fossil records indicating dinosaurs of the Jurassic period suffered from the disease. The Greek physician, Galen is accredited with describing human tumours of having the shape of a crab, with leg like tendrils invading deep in to surrounding tissues, hence the term cancer. Today cancer can be defined as any malignant growth or tumour caused by abnormal and uncontrolled cell division, able to invade tissues locally and have the ability to spread to other parts of the body through the lymphatic system or the blood stream. This is obviously a simplistic attempt at describing a complex disease that can utilize a myriad of biological pathways to sustain growth and proliferation. Dissecting these pathways has been the challenge of cancer researchers for decades in the search for new treatment strategies. This review attempts to condense our understanding of cancer and offer insights into an alternative theory regarding the existence of true cancer stem cells and how this will inform the development of new therapeutics.
Fundamental to our basic understanding of mammalian physiology is the concept of homeostasis. If we consider the body as a multi-cellular unit, then cells within this unit form part of a specialized society that cooperates to promote survival of the organism. In terms of homeostasis, cell division, proliferation and differentiation are strictly controlled and a balance exists between normal cell birth and the natural cell death. In simple terms, cancer can be considered as a breakdown in cellular homeostasis leading to uncontrolled cell division and proliferation, which ultimately leads to a disease state.
The mechanisms of this breakdown are the subject of intense research, especially considering the high incidence of cancer in both humans and domestic animals. However, despite the fact that cancer is a common disease and considering the number of cells making up an organism, the change from normal cell to cancer cell is actually a very rare event. This is because evolution has allowed the development of many fail-safe mechanisms within the cell that react to DNA damage by arresting the cell cycle (to allow repair) or allowing the cell to die naturally. In this short synopsis of cancer biology we will consider our current understanding of cancer biology and discuss some of the ways that this understanding is leading to informed drug development. Further, we will consider the role of Stem Cells in cancer and how they are challenging conventional wisdom.