Biology of cancer

Cancer is considered a genetic disease. In the context of cancer, the term “genetic disease” refers to the fact that cancer arises from genetic alterations or mutations in the DNA of cells. These mutations can occur due to a variety of factors, including environmental exposures, lifestyle choices, and inherited genetic predispositions.

There are two main types of genetic alterations that contribute to cancer development:

1) Somatic mutations

These are genetic mutations that occur in the DNA of somatic cells (non-reproductive cells) during a person’s lifetime. Somatic mutations can result from exposure to carcinogens, such as tobacco smoke or ultraviolet radiation, or from errors that occur during DNA replication or repair. These mutations can lead to the uncontrolled growth and proliferation of cells, characteristic of cancer.

2) Germline mutations

These are genetic mutations that are present in the DNA of germ cells (sperm or egg cells) and can be passed down from parents to their offspring. Inherited germline mutations can increase an individual’s risk of developing certain types of cancer. While inherited mutations may not directly cause cancer, they can predispose individuals to the disease by increasing their susceptibility to other genetic or environmental factors that promote cancer development.

It’s important to note that not all cancers are solely caused by genetic factors. Many cancers arise from a complex interplay of genetic, environmental, and lifestyle factors. Additionally, not all genetic mutations lead to cancer; some may have no effect, while others may cause different types of diseases or conditions.

Cancer usually develops over a period of many years. This is because it involves a series of genetic (and epi-genetic) changes that lead to the transformation of a normal cell into malignant cancer cells and a full blown metastatic disease. Epigenetic changes refer to modifications, not mutations, of the DNA sequence of genes that regulate their expression. For example, DNA methylation can switch off gene expression and thereby affect various crucial biological processes, including cancer.

The transformation of a normal cell into a cancer cell is known by several terms, such as oncogenesis, tumorigenesis or carcinogenesis. The accumulation of multiple mutations in so-called oncogenes or deletions in tumor suppressor genes that are of key importance in regulatory mechanisms controlling cell growth, proliferation, differentiation, and death, are at the basis of a stepwise increasing cellular malignancy. At later stages a proportion of tumor cells are able to leave the primary tumor and disseminate to other tissues and form metastases, or secondary tumor lesions. For example, lung cancer cells (primary tumor) often metastasize to lymph nodes, liver, bones and the brain. It is interesting to note that different tumor types have different tissue preferences for forming secondary tumors. Factors such as blood supply, oxygenation, immune response, and the presence of growth factors or signaling molecules in the microenvironment may influence whether metastatic tumor cells can thrive and proliferate in a particular organ.

Oncogenes & tumor suppressor genes

As mentioned, the process of oncogenesis is complex and can involve various genetic, epigenetic, and environmental factors. It often requires the cooperation of multiple oncogenes (genes that promote cancer development) and tumor suppressor genes (genes that inhibit cancer development) to overcome the body’s normal regulatory mechanisms.

The normal version of an oncogene, named proto-oncogene, usually plays a role in the regulation of cell growth, whereby its oncogenic version leads to signals in a cell that instructs it to continuously replicate its DNA, divide and proliferate. On the other hand, tumor suppressor genes act to balance or counteract the activity of proto-oncogenes/ oncogenes, by for example inhibiting cell proliferation or instructing a damaged cell to die by activating a so-called programmed cell death mechanism, known as apoptosis. An analogy with driving a car is often used to illustrate the activity of these genes, oncogenes being the gas pedal, and tumor suppressor genes the brakes.

Image courtesy of the National Cancer Institute

Tumor suppressor genes are recessive genes and some mutated alleles are inheritable. That is why in some families specific cancer types occur more frequently than normal, because the tumorigenic process is already partially initiated at birth resulting in cancer at relatively young age.

In addition to mutations, the products of genes, the proteins, can also be inactivated by specific viruses that produce proteins that can bind to and inactivate tumor suppressor proteins. In this way infection with these viruses increases the likelihood to develop cancer. A well-known example of such a virus is HPV, human papillomavirus. Although the identification of oncogenes and tumor suppressor genes greatly aided our understanding of cancer drivers and provided avenues for developing new therapies, there is still much more to learn about the factors underlying cancer initiation and progression. This will be addressed in the next part, Hallmarks of cancer