What Causes Cancer?

Most, if not all cancers are caused and perpetuated by a small population of tumor-initiating cells that exhibit numerous stem cell-like properties. Adult stem cells (SC) are involved in the regeneration and maintenance of our body tissues and account for one out of every 6 million cells. Each tissue has a unique population of specific SCs located in regions known as niches. In the SC niche, the SCs exist in a unique dormant state known as quiescence, and remain in this state until they are given the cues to be activated.

Activated stem cells go through two stages of development referred to as proliferation and differentiation. During proliferation, biochemical cues cause the cells to reproduce, resulting in an expanded population of similar cells. Differentiation puts a stop to proliferation with specific biochemical cues that cause the proliferating cells to differentiate into a specific type of cell. Once a stem cell has differentiated, it has a finite life span and is limited in how many times it can reproduce. The number of times a differentiated cell can reproduce is referred to as its Hayflick number. SEE BELOW

Diagram of Normal Stem Cell Activation


Cancer results when a stem cell is stuck in proliferation, and is therefore not given the cues to differentiate. This situation results in a continually expanding population of undifferentiated cells that can not only exist anywhere in the body (metastasis), but also have unlimited life spans (no Hayflick number). SEE BELOW

Diagram of Cancer Initiating Stem Cell Activation


The biochemical cues for proliferation and differentiation are based on genes specific to each tissue type. In general, genes that initiate proliferation are called oncogenes while genes that initiate differentiation are called tumor suppressors. Cancer, therefore, could be seen as an over-activation of oncogenes accompanied by the inhibition of tumor suppressors. It is the ratio of oncogenes to tumor suppressors that determines the aggressiveness of the cancer.

Another key piece in the growth of cancers is a process called angiogenesis. Angiogenesis is the physiological process that tumors use in order to recruit new blood vessels in order to sustain their continual growth. They do this by over-expressing genes that initiate and direct the growth of new, leaky blood vessels from existing ones. Both angiogenesis and the spontaneous formation of new blood vessels (vasculogenesis) are initiated by unique combinations of genes.

Standard chemotherapeutic agents inhibit rapidly dividing cells during treatment, but do not affect dormant cancer initiating SCs. An example of this is shown in a side affect of treatment. During chemotherapy, patients lose their hair (rapidly dividing cells), but their hair typically grows back soon after treatment.  This is due to the dormant SCs located in the hair shaft, which were not affected by the chemotherapy. It is this presence of dormant cancer initiating SCs combined with the occurrence of angiogenesis in-between treatment regimes that leads to disease recurrence.

The following link allows you to identify the genes involved with various types of cancers.

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