Researchers at the Spanish National Cancer Research Centre (CNIO), Manuel Hidalgo, Director of the Clinical Research Programme, and Manuel Serrano, Director of the Molecular Oncology Programme, have both been awarded Advanced Grants by the European Research Council (ERC). Each of them will receive 2.5 million euros to address three of the major challenges in European biomedicine, namely cancer research, personalised medicine and the study of ageing, and to advance the frontiers of knowledge from a creative and innovative perspective. These grants are amongst the most prestigious awards of their kind in Europe, this is the second time in a row that Serrano has won this award.
Furthermore, the young researcher Alejo Efeyan has been awarded the prestigious ERC Starting Grant for young investigators (with less than 7 years of postdoctoral experience) and he will receive 2 million euros for the creation of a new research team with “excellent ideas”, as defined in the ERC Call. Currently a Postdoctoral Associate at the prestigious Massachusetts Institute of Technology (MIT) in the USA, Efeyan will develop his ERC project at the CNIO in January 2016.
AVATARS FOR PERSONALISED CANCER TREATMENT
Hidalgo’s team will address new personalised treatments for pancreatic cancer, a type of tumour that is expected to become the second most common cause of death from cancer by 2020, after lung cancer, and for which, to date, there are no specific treatments.
Pancreatic cancer is a complex and heterogeneous disease where the cells may harbour hundreds of mutations, which differ from patient to patient and which can affect drug responses. The researchers’ main hypothesis is based precisely on this genetic variability, which may be useful for the individualised treatment of patients, as has been demonstrated in other tumour types, such as breast cancer or melanoma.
In a first initial phase, the researchers will analyse the genetic signature of patients’ tumours in order to select the mutations that are particularly relevant for growth and progression. In a second phase, they will use the so-called avatar mice — which carry implanted fragments of the patient’s tumour — in order to evaluate the potential efficacy of treatments based on the genetic signature of each individualised patient. The treatment that is most effective in the avatar mice will be administered to the patient.
This ambitious project will be carried out in a clinical trial involving more than 150 patients, selected from the CNIO’s collaborative network of public hospitals. “We hope to obtain knowledge on the molecular basis of the disease that will have a direct impact on improving treatment,” explains Hidalgo.
REGENERATIVE MEDICINE, CANCER AND AGEING
In turn, Serrano and his group will be studying cellular plasticity — the capacity of cells to change their identity and transform themselves into a different type of cells — in order to gain further knowledge about pathologies such as cancer or ageing, or organ regeneration.
According to Serrano: “We believe that cellular plasticity has two pathological variants: cancer as a result of an aberrant excess of cellular plasticity, and ageing as a result of exactly the opposite, that is loss of cellular plasticity.”
The core of the research will focus on the mouse created in 2011 by the same group of researchers, in which for the first time, cells in a primitive state were obtained directly within a living organism. The results were reported in the celebrated journal Nature (http://www.cnio.es/es/news/docs/manuel-serrano-nature-11sep13-en.pdf) and were considered as Notable Advance of 2013 in regenerative medicine by the journal Nature Medicine.
EXCESS OF NUTRIENTS
An excess of nutrients is associated with human pathologies such as obesity, diabetes or even cancer. In this regard, it has been known for over a decade that the mTOR protein acts as an orchestra conductor, and it becomes active under these conditions to promote cell growth.
“We know that there are some cellular mechanisms in which mTOR facilitates these processes, however, we do not know what the consequences would be if they were manipulated in higher living organisms such as mammals,” says Efeyan. In order to gain more knowledge in this area, his team at the CNIO will study these processes in mammals for the first time, using mouse models.
Rapamycin is currently one of the most popular drugs used to block mTOR action and, as a result, impair cell growth and proliferation. For this reason, it may be useful in treating some types of cancer. “The problem with this drug is that it can alter some metabolic activities in cells, which is why this is an extremely active field of research.”
In the long term, the researcher’s goal is to join efforts with national and international laboratories to discover new molecules that will specifically block mTOR, or the chain of events that it triggers within cells.
About the ERC
Set up in 2007 by the EU, the European Research Council is the first European funding organisation for research on the frontiers of knowledge. The ERC operates according to an 'investigator-driven', or 'bottom-up', approach, allowing researchers to identify new opportunities in any field of research, without thematic priorities. Every year, it selects and funds the very best, creative researchers of any nationality and age to run five-year projects based in Europe. Since its launching, the ERC has funded over 5,000 researchers. Under Horizon 2020, the new EU research programme (2014-2020), the ERC has a budget of over €13 billion.