Only a few years ago it was thought the cells in a tumour were genetically identical. However, recent technological breakthroughs in this field have shown that this is not the case. Thus, it is now known that different families of cells in any one cancer share some mutations but also present other specific mutations. “Indeed, there are several cancers to be treated inside a cancer”, summarises Lorenzo Melchor, one of the speakers at the seminar on cancer genomics organised today by the Biomedical Research Institute (IBI) in the framework of the BIOCAPS project.
The scientists from Spanish and UK centres who came together this morning in Vigo agree that genome sequencing techniques are the ideal tools for unravelling the complex web of cells and mutations that differs for each type of cancer and in each patient. Its future application in diagnosis and treatment will allow the personalised approach required for tumour-related conditions.
This will be possible as sequencing technologies allow the genome of cancer cells to be studied in detail. As cancer is actually a combination of genomic diseases, an ability to determine which changes are responsible for the disease in any one patient is essential. In a good analogy, Javier Herrero, coordinator of the genomic data analysis node at the UCL Cancer Institute (London), notes that “if the fight against cancer were a game of cards, sequencing the genome for each cancer would be like having a look at the cards held by your opponent”.
An understanding of the causes of each cancer and how it has managed to evade the control mechanisms found in our cells is possibly the greatest challenge faced by the biomedical community. In this regard, Herrero and his team are concentrating on leukaemia and using genome sequencing techniques to study tumour cells, especially those resistant to current treatments.
These mechanisms of resistance to antitumour agents are one of the main bones of contention amongst scientists. Ignacio Varela, from the Institute of Biomedicine and Biotechnology of Cantabria, who studies intra-tumour heterogeneity, the term used to define the presence of several genetically distinct cell populations within a single tumour, is fully aware of this. Indeed, Varela's team has observed that these populations interact with each other to form a constantly evolving ecosystem in which the most efficient populations survive and dominate the territory whereas less efficient populations are limited to specific regions of the tumour. “However, it has been seen that the latter are probably responsible for the generation of metastases or are the most resistant to treatment. In this case, these minority populations, which are much more difficult to find and study, present the greatest danger to the patient's life”, explains Varela.
In the opinion of this researcher, the application of genome sequencing techniques to cancer management in clinical practice will be key to designing the therapeutic strategy with the greatest likelihood of success for each particular patient and significantly improving their response to treatment. “These techniques allow us to study all the patient's DNA and discover new regions or alterations that may be of importance in each specific case. They also provide much greater sensitivity and allow us to detect different responses to treatment in different regions of the tumour”, he notes.
Darwin and natural selection in cancer
Lorenzo Melchor, from the Institute of Cancer Research, is testing an innovative approach to cancer research that involves applying Darwin's theory of natural selection to solve some of the questions regarding the source, development and evolution of this disease. Specifically, Melchor and his team are concentrating on myeloma or bone marrow cancer, which is characterised by the uncontrolled growth and dysfunction of plasma cells, our antibody factories. This cancer is currently incurable, with a positive response to treatment in many patients in the early stages but the subsequent onset of resistance that makes its evolution unstoppable.
“In the past four years we have shown that multiple myeloma in a patient contains at least four or five families of tumour cells and we have seen that these families respond differently to treatment”, he explains. The identification and study of those resistant to the effect of anticancer drugs and which, therefore, lead to relapse in the patient is now a prime objective. “There is still a great deal to discover”, he notes.
Collaboration and a multidisciplinary approach
José Manuel Tubío, from the University of Cambridge, explained the role of the PanCancer initiative, an international effort in which hundreds of scientists from dozens of countries are participating and which is promoted by the two most important consortia dedicated to cancer genomics in the world: the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). “This is one of the most interesting challenges in research into this disease worldwide. In less than two years we aim to identify all the genetic mutations present in more than 2000 cancer genomes”, he explains.
“My contribution to this initiative is to analyse the structural variants of cancer, in other words those mutations that affect large segments of the chromosome.” The success of this effort, which has been given the name PanCancer, lies in a collaboration between expert researchers from different fields of knowledge (biologists, mathematicians, physicists, etc.) and the sharing of the data generated, which will result in a large body of integrated knowledge concerning multiple types of cancer and, consequently, faster and more efficient progress in research in this field.