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When new research comes to light related to Cancer At least two questions usually surface: Can we cure cancer? What does this study mean for patients diagnosed with cancer?
The answer is complicated. However, thousands of researchers are dedicated to studying this disease with the aim of being able to, at least, have an answer. For this reason, cancer is currently the main biomedical challenge that both health and scientific personnel face.
Thorough knowledge of human tumors
In recent years, one of the main advances in the scientific community has been the sequencing of the genome of different human tumors. What does this imply? Know the gene instructionsethics possesses a tumor cell to develop.
Recent genome sequencing studies have revealed that cancer is made up of thousands of genetic alterations (called mutations) in a large number of genes.
However, in order to address such relevant issues as, for example, the design of antitumor drugs, it is not enough to describe these alterations. It is necessary to know which mutations are really important for the development of cancer and, at the same time, to know what effects they cause. This is one of the current challenges of biomedicine.
Specific, VAV1 is one of the genes that is mutated in different types of tumors. Mainly, in a tumor that originates in blood cells that is known as peripheral T-cell lymphoma.
T cells (also called T lymphocytes) are cells of our immune system that recognize and destroy other cells that are potentially “dangerous” to our body. For example, cancer cells or cells infected by various types of viruses, such as the one that causes Covid-19. However, the problem arises when the T lymphocytes themselves suffer mutations that cause them to proliferate uncontrollably and promote the formation of lymphomas.
The danger of mutations in T lymphocytes
A research group from the Salamanca Cancer Research Center has spent years studying the role of VAV proteins in cancer. It is a family of proteins that we now know play relevant roles in the formation of many types of tumors, such as skin or lung cancer.
This experimental evidence alerted us to the importance that the alterations described for the VAV1 gene could have in the development of peripheral T-cell lymphomas. Having a better understanding of the role that these mutations play in the biology of cancer, we could establish most effective therapeutic strategies.
If VAV1 activation is adequate, the T lymphocytes function normally. This is the ideal scenario. However, if this activation is wrong, the cells begin to grow and divide in an uncontrolled way. This is the case in the case of peripheral T-cell lymphomas.
As described in the work published by this research group in the scientific journal EMBO Journal, most of the mutations found in patients lead to uncontrolled activation of the VAV1 protein in cancer cells. In this way, we know that they are relevant for the development of tumors.
Furthermore, our data revealed that not all mutations have the same effect on VAV1. Rather, we have classified these mutations into several subtypes depending on the degree of impact they had on the protein. This could indicate that each of these subtypes may be associated with different pathological and clinical characteristics in patients.
We have also shown that the most frequent mutations of VAV1 act as fully autonomous oncogenic “drivers”. Namely, are capable of inducing tumors without the need to appear with other genetic alterations. This observation further underlines the fact that the presence of these mutations in tumors is not trivial. They are the main responsible for their origin.
Mice may give us the answer
Peripheral T-cell lymphomas are characterized by their aggressiveness, lack of therapeutic options, and high mortality that has not improved significantly in recent years. These tumors constitute, therefore, an important challenge at the clinical level.
For this reason, the current use of mice as preclinical research models has meant a huge leap in quality in advances in oncology. The aforementioned work has developed an animal model that allows the generation of lymphomas in mice after the expression of VAV1 mutants in healthy T lymphocytes.
With the use of genomic and bioinformatic techniques, it has been observed that said animal model generates T-cell lymphomas that are very similar to those found in patients. These lymphomas reproduce the vast majority of the clinical, pathological, and molecular features of patient lymphomas.
It also allowed to discover the weak points or Achilles heels of these lymphomas. These could be used to find different ways to attack and destroy these tumors. For example, these therapeutic strategies could be aimed at inhibiting activation pathways involved in proliferation or interfering with the metabolism of tumor cells.
Finally, these animal models will also be an exceptional way, from now on, to test the effectiveness of drugs preclinically. This is especially relevant in this type of tumors, given the difficulty that has existed until now to classify, study and treat them effectively.
This is now the most important challenge we face. These new contributions open a path to follow for drug development. Without having this information, it will not be possible to address the implementation of a personalized medicine routinely in hospital.
It is not an easy path and it will take even longer than we would like, but it is an interesting roadmap to block the development of this type of tumor, among other cancers.
Javier Robles Valero. Senior Researcher at the Cancer Research Center – Professor of Biochemistry, University of Salamanca.
This article was originally published on
The Conversation.