What is cancer?
It is a class of diseases characterized by out-of-control cell growth. There are over 100 different types of cancer, and each is classified by the type of cell that is initially affected.
It harms the body when altered cells divide uncontrollably to form lumps or masses of tissue called tumors (except in the case of leukemia where cancer prohibits normal blood function by abnormal cell division in the blood stream). Tumors can grow and interfere with the digestive, nervous, and circulatory systems, and they can release hormones that alter body function. Tumors that stay in one spot and demonstrate limited growth are generally considered to be benign.
More dangerous, or malignant, tumors form when two things occur:
1. A cancerous cell manages to move throughout the body using the blood or lymphatic systems, destroying healthy tissue in a process called invasion
2. That cell manages to divide and grow, making new blood vessels to feed itself in a process called angiogenesis.
When a tumor successfully spreads to other parts of the body and grows, invading and destroying other healthy tissues, it is said to have metastasized. This process itself is called metastasis, and the result is a serious condition that is very difficult to treat.
According to the American Cancer Society, It is the second most common cause of death in the US and accounts for nearly 1 of every 4 deaths. The World Health Organisation estimates that, worldwide, there were 14 million new cases and 8.2 million cancer-related deaths in 2012 (their most recent data).
Scientists at Karolinska Institutet in Sweden report thatcancer cells and normal cells use different ‘gene switches’ in order to regulate the expression of genes that control growth. In mice, the removal of a large regulatory region linked to different types of cancer caused a dramatic resistance tumour formation, but did not affect normal cell growth. The findings, published in the scientific journal eLife, highlight the possibility of developing highly specific drugs with fewer side effects.
Humans have close to 20,000 genes to carry out all the functions in a cell. The genes make up only 2 per cent of a cell’s total DNA. What makes us different from one another is mainly the variation in the remaining 98 per cent of our DNA. The variation is believed to alter the activity of regulatory regions or ‘gene switches’ (enhancer elements), which control the activity levels of genes in a cell. It is this variation that is mainly responsible for making individuals more or less susceptible to the development of diseases such as cancer.
In the current study, using mice, scientists have analysed a large gene switch region that is linked to the risks of developing many different types, including prostate, breast, colon, bladder and thyroid cancers as well as chronic lymphocytic leukaemia and myeloma. The variation in this region accounts for far more cancer-related deaths than inherited mutations in well-known cancer-causing genes. It is currently unclear why the cells use these particular switches, and whether they have any function in normal cells.
The scientists turned the gene switches off by removing this region from the mouse genome, and found that its loss has no effect on normal mouse development and growth. Although removing the gene switch region brought down the levels of the nearby cancer gene Myc, the mice remained normal and healthy. However, the mice were strongly resistant to the formation of breast tumours and tumours in the intestine.
According to the scientists, these results show that normal cells can function and divide without the genetic elements that are needed for the growth of cancer cells. The study therefore highlights the possibility of developing highly specific cancer drugs.
“Since we find that the growth of normal and cancer cells is driven by different gene switches, we can in principle aim at switching off the system for growth only in the cancer cells without any harmful effect on the growth of normal cells. This can lead to the development of highly specific approaches for the therapy with much lower toxic side effects”, says Professor Jussi Taipale at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics who led the study.
The research work was supported by the Center for Innovative Medicine at Karolinska Institutet, the Knut and Alice Wallenberg Foundation and the EU FP7 Health project SYSCOL.