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Los investigadores del CNIO Alejo Efeyan (Izda.) y Nabil Djouder. /A. Tabernero. CNIO
Regarding cancer prevention and food, the recommendation is to avoid obesity and alcohol, as well as eating plenty of vegetables and reducing red meat and processed food. However, on a molecular scale, it is not yet understood why one diet is better than another.
In recent years, nutrition has been observed to play a possible role in cancer treatment, as well as in prevention.
However, there is still a lack of knowledge as to include diet as part of cancer treatment. CNIO Researchers Nabil Djouder and Alejo Efeyan are working towards this goal.
What we eat and drink influences the incidence, growth and progression of cancer, to the extent that diet can help to prevent a third of the most common tumours. The International Agency for Research on Cancer (IARC) points out that “there is solid evidence that a healthy diet and physical activity reduce the risk of cancer”.
More specifically, regarding diet for cancer prevention, the IARC recommends: avoiding obesity; limiting alcohol, sugary drinks and highly processed food; consuming more vegetables and less red and processed meat.
However, in recent years, there has been a “paradigm shift”: nutrition may also play a role in cancer treatment, not only in its prevention.
As the researcher at the Spanish National Cancer Research Centre (CNIO) Nabil Djouder explains, “various pre-clinical studies [on animals] using healthy food as an anti-cancer tool have shown promising results and, conversely, other studies have proven that unhealthy food may accelerate the development of certain types of cancer”.
Research to take nutrition to the clinic
However, not enough is known yet to integrate diet in cancer treatment as another therapeutic element. “The results have not been taken to the clinic as we are yet to understand the molecular mechanisms behind them”, adds Djouder. “It has been shown both in mice and in clinical trials on humans that food may increase or decrease the risk of cancer, but we need to understand how this occurs inside the cells for this information to be translated into therapies”.
Two CNIO groups are working to unravel the diet-related molecular mechanisms that influence a cancerous process: the Growth Factors, Nutrients and Cancer Group, led by Djouder, and the Metabolism and Cell Signalling Group, led by Alejo Efeyan.
Diet and Metastasis
Djouder researches these mechanisms in metastasis: “We are trying to see how different diets – high sugar, ketogenic (very low in carbohydrates, high in healthy fats and moderate levels of protein), high fat, high protein, low calorie or intermittent fasting, etc. – influence metastasis. Once we have established whether they are influential or not, we will study the molecular mechanisms that are activated by them”.
Metastasis is the process by which the primary tumour colonises other parts of the body, and is responsible for the majority of cancer-related deaths. ‘For this reason, it is so important to understand how diet can influence its development”, according to Djouder.
Different metabolism in tumour cells
In a recent review, Djourder has analysed what is currently known about the use of diet in cancer treatments. He explains that “diets can directly target cancer metabolism, by depriving the tumour of the nutrients it needs, or they can affect other key elements for cancer survival and development, such as growth signalling, oxidative stress or patient immunity”.
His group studies metabolism, biochemical processes that occur in the cells and which transform nutrients into the energy we need. In cancer cells, the chemical reactions involved in metabolism are quite different.
Diet to boost immunotherapy?
“Finding a diet that can influence metastasis and understand its molecular mechanisms would be really important, as it would enable us to suggest diets associated with cancer treatments”, continues Djouder. “When I say influence, I am referring to a diet that positively or negatively affects the progression of metastasis, the survival of the patient, or that helps to reduce the effect of the metastasis”.
There are also certain metabolites – substances that the body produces when processing food – that may influence and have a positive or negative impact on the immune system, leading to the prevention or development of tumours or metastasis.
Investigating these metabolites and understanding how they work, especially in other cells, is key to the research that Djouder is undertaking in his laboratory. The beneficial metabolites could be used in conjunction with treatments such as immunotherapy or chemotherapy to fight against the tumour more effectively.
Deciphering the dialogue between cells
Alejo Efeyan’s group tries to understand which metabolic processes have a greater effect on tumour cells than normal cells, when these processes occur and how. The group hopes that this knowledge will enable them to act to treat the tumour cells selectively and powerfully without damaging the patient’s other cells.
They are investigating the so-called signalling cascades, the interaction networks that are activated in the cells in response to certain stimuli, such as certain nutrients. “We know that cancer cells tend to like the excess of nutrients and energy. We are trying to gain an insight into which genes and proteins participate in these alterations”, explains Efeyan.
There are many metabolic processes that influence the behaviour of normal and tumour cells, as well as their interactions, their dialogues; “only by dissecting the components one by one will we be able to understand what is happening”, assures the Head of the Metabolism and Cell Signalling Group at CNIO.
“We know that tumours send certain signals to their surrounding cells. If we are able to detect, tumour by tumour, which metabolites the cancerous cells like so much, we will probably generate new therapeutic tools. These may be different types of diet or pharmacologic interventions, i.e. new drugs that are capable of interrupting this communication. To do so, we are studying the molecular mechanisms that are produced in tumour cells and in the surrounding non-tumour cells which send and receive metabolites to and from the cancerous cells”, explains Efeyan.
Caloric restriction and cancer
One of the most active areas of research is how caloric restriction diets and intermittent fasting affect the progression of tumours. Several groups have observed promising results, but Efeyan highlights the problem: “we know that these diets are more difficult to stick to”, and more knowledge is required to transfer what has been learnt to date to the clinic.
“We know experimentally that some alterations may be corrected when introducing a type of caloric restriction but not another. There are diets that work well with some tumours but not with others, and this heterogeneity also occurs in tumour cells in the same patient. For this reason, we need to understand which molecular mechanisms are behind each of these reactions. Only then will we be capable of intervening in the limitation or contribution of certain nutrients depending on the type of specific tumour, and according to the type of patient being treated”, concludes this researcher.