Advances in the area of genomics revolutionize the treatment of cancer

Rogelio González-Sarmiento, of the University of Salamanca Cancer Research Center relates how advances in sequencing techniques and gene expression profile analysis are enabling the planning of personalized therapy strategies.

By Karina Toledo, from Salamanca

Agência FAPESP - Scientists have long known that cancer is a genetic disease, in other words, the result of an accumulation of genomic alterations caused by aging, hereditary factors or by external agents like radiation and tobacco.

Only in recent years, however, thanks to the development and cost reductions of sequencing methodologies and gene expression profile analysis have scientists been able to uncover the specific alterations behind each tumor.

With this information in hand, physicians are able to predict, for example, a tumor’s degree of aggressiveness, its ability to spread to other organs and its sensitivity to certain types of drugs – which the planning of new personalized therapy strategies.

The topic was addressed by researcher Rogelio González-Sarmiento, of the University of Salamanca (Usal) Cancer Research Institute this Tuesday (12/11), during the “Frontiers of Science – Brazil and Spain in the 50 years of FAPESP” event.

The “Frontiers of Science” event includes the celebration of 50 years of FAPESP in the cities of Salamanca (12/10-12/12) and Madrid, 12/13-12/14), and brings together researchers from the state of São Paulo and from several academic and research institutions of Spain in a lively and varied program that is open to the public.

“The new generation sequencing techniques have allowed researchers in laboratories to redefine tumor classifications on the basis of molecular characteristics. This paradigm shift is modifying the therapeutic strategy used by oncologists,” he asserted.

Epigenetics

In addition to genetic alterations themselves – which are those that undergo modification in the DNA sequence, such as point mutations, deletions, insertions and chromosomal rearrangements – the epigenetic alterations may also cause cancer, said Manel Esteller, director of the Epigenetics Program of the Bellvitge Biomedical Research Institute in Barcelona.

“Let’s imagine that the genome is our computer hardware and that epigenetics is the software that makes the hardware work.,” Esteller told Agência FAPESP.

That is why, the researcher adds, identical twins are able to develop different diseases despite sharing the same DNA. “They have the same hardware, but different software. They are chemical alterations that regulate gene expression.”

The most important of the known chemical alterations is DNA methylation, a reaction that involves the addition of a methyl group (CH3) to certain parts of the DNA, which effectively changes the pattern of gene expression.

“It is a physiological process of gene regulation. For example, our brain cells have the same DNA as our heart cells, but they have different functions. To a large extent, this occurs thanks to DNA methylation. What happens in cancer is that there is an overall change in DNA methylation that creates a corrupt software,” Esteller explained.

According to the researcher, what causes epigenetic alterations is very similar to what is responsible for modifying the DNA sequence. The most important among them, said Esteller, is aging.

“It is possible to measure a person’s biological age by analyzing her DNA methylation profile. As we go through life, we have experiences that change our cells. The process of DNA methylation begins to diminish and leaves the chromosomes more fragile and easily corrupted,” the researcher explained.

Only a few genes – and they are precisely those responsible for protecting us against cancer – undergo more methylation due to aging and have their expression blocked. “Today, the main risk factor for cancer in developed nations is age.”