Knowing the enemy

2012/05/01 Rodríguez, Jose Antonio - EHUko Genetika, Antropologia Fisikoa eta Animalien Fisiologia Saileko irakaslea Iturria: Elhuyar aldizkaria

• Medikuntza

In December 1971, US President Richard Nixon signed the National Cancer Act. This new law was called "declaration of war against minbiacia" by journalists. In this war we are still immersed forty years later. However, today we know our enemy much better.

Humans, as multicellular beings, carry the cancer seed in our cells.

This seed is based on the ability of our cells to communicate, reproduce and migrate from one place to another. These capabilities are fundamental to human development, growth and survival. But the cellular mechanisms that make our life possible, malfunction, can promote the development of cancer. For example, cells in an embryo use the same mechanisms to form parts of the body and cells of a tumor to develop metastases.

Cancer is a genetic disease. Alterations in cell proliferation, communication and migration are the result of errors in the genome. These errors can alter the marks that determine genetic information or the use of genetic information (mutations and epigenetic variants, respectively). In many cases, errors arise spontaneously when the cell copies its DNA. Other times, defects can be produced or facilitated by an external agent, such as mutagenic tobacco fumes or virus infections.

Cancer research has long tried to answer two basic questions. What type of alterations does a normal cell undergo until it becomes an invasive tumor, that is, how the transformation process occurs? And what are the genomic variants that favor this tumorigenesis process?

In this search for answers, important steps have been taken since President Nixon declared the "war on cancer." As for the first question, in the 1970s it was proposed that tumorigenesis is a process in stages and that under progressive transformation are the clonal extensions of cells. According to this model, clonal extensions occur when a cell gets a new feature that gives it a growth advantage over adjacent cells. The new feature can be, among other things, the ability to split faster or without limits.

Regarding the second question, XX. During the last two decades of the 20th century, several genes related to the development of cancer were identified. These "cancer genes" are classified as "oncogene" or "tumor suppressor gene" based on their function. The alteration of these genes, as a result of mutations or epigenetic variants, allows tumor cells to carry out a clonal expansion. In many tumors, for example, abnormal expression and activity of the telomerase gene boosts unlimited cell fragmentation capacity. On the other hand, it was long established that the tumor cell genome is unstable and it is known that this instability facilitates the accumulation of mutations.

In recent years cancer research has received a remarkable boost. In this new impulse two advances have been fundamental: the sequencing of the human genome and technological developments. The first draft of our genome was published in 2001. This information allowed researchers to obtain a reference to identify genomic defects that build up in tumors. In addition, the Human Genome Project began to develop new genomic analysis technologies.

From a technological point of view, the most important developments are occurring in DNA sequencing methods. Currently, a man's entire genome (or tumor) can be sequenced within two weeks. Using this technological capacity, an international project called the International Cancer Genome Consortium (ICGC) has been launched. The aim of this project is to sequence thousands of tumor samples of different types. In addition to sequencing, other large-scale analysis methods have been developed. These methods, such as transcriptomic or proteomics, improve year after year, and each improvement facilitates and accelerates research.

As a result of all these advances, the knowledge of the tumorigenesis process is being sharply deepened. Although the classic clonal expansion model maintains its value, new studies have shown that the complexity of tumors is much greater than what is believed - both at the cellular and generic level. For example, some types of tumors have identified “cancer stem cells,” which have the ability to regenerate the tumor after treatment. It has also been shown that tumor development may involve not only tumor cells but also normal micromedia cells. The ICGC project has already discovered thousands of new mutations. Some mutations are a consequence of the genomic instability of the tumor, others favor the transformation process, so they can be used to identify new "cancer genes".

Clinical research tries to use this basic knowledge to improve cancer prevention, detection, diagnosis, and treatment. For example, based on genetic errors in tumors, "corrected" therapies are being developed, which have a higher impact and a lower side effect.

More than two thousand years ago, Chinese writer Sun Tzu wrote in his book The Art of War: "If you know your enemy and yourself, you can win hundreds of battles." Several battles have been won in the war against cancer. Knowing the enemy more and more gives us hope for more victories.