Innovative approaches to making cancer cells extinct
Cancer closely follows the rules of nature and natural selection. Just as when stress in the environment is introduced and species adapt, cancer does the same thing. “When a tumour arises, it finds itself in a hostile environment, and its survival depends on its capacity to adapt,” explains CancerADAPT(opens in new window) project coordinator Arkaitz Carracedo from CIC bioGUNE(opens in new window) in Spain. “But while species evolution takes thousands and thousands of years, cancer adapts in a matter of months.”
Targeting cancer cell metabolism
The focus of the CancerADAPT project, which was supported by the European Research Council(opens in new window), was to identify and target this ability of cancer to quickly adapt and thrive. In particular, the team wanted to find out how cancer cell metabolism – the biochemical conversion of molecules – might evolve at each stage of cancer progression and shed light on the role this could play in tumour survival. “We wanted to picture this short time frame of evolution, to understand which treatments might help to prevent cancer cells from surviving,” says Carracedo. “In nature, to force extinction is to deny an organism the capacity to adapt, and this was our goal here.”
‘Snapshots’ and ‘videos’ of disease progression
The team adopted three broad strategies. The first was to acquire or analyse available patient samples (mostly of prostate cancer) at different stages of disease progression. “While patient samples provide a snapshot of the disease at a given time, we can incorporate clinical patient information to know how the tumour behaved after diagnosis or treatment (whether the patients recovered or not),” adds Carracedo. “By applying bioinformatic techniques, we attempted to identify the processes and genes related to recurrence and metastases.” Second, the project team developed experimental models in which they could control the timing of disease progression. “Mouse models provide us with a video rather than a snapshot, since we can monitor the manifestation and progression of the disease in real time,” notes Carracedo. Finally, the project studied cancer cell metabolism at the molecular level, to better understand the hidden language of cancer cells, and their means of interacting with the host organism proteins involved, and to see how cancer cells ‘communicate’ with the rest of the body.
Progress on aggressive forms of cancer
Impressive progress has been made on a particularly aggressive form of prostate cancer, responsible for around 5 % of cases but 50 % of prostate cancer deaths. The team was able to shed new light on the molecular differences that enable this type of cancer to develop so rapidly. This will now be the subject of further research. Furthermore, the experimental models pioneered by CancerADAPT have been scaled up to a preclinical platform. This will enable the testing of drugs and molecules that target cancer cell adaptation. “We also identified metabolic enzymes that can help to tell us if a patient is likely to develop a metastasis in 10 years,” says Carracedo. “What is fascinating is that these enzymes are expressed by normal cells living within the tumour, not cancer cells.” This underlines how the ecosystem is a determining factor in disease aggressiveness, through enabling communication between tumour cells and the body’s immune system. New insights were also gleaned on how metabolites and proteins communicate, and how this might help cancer cells to adapt and thrive. All this groundbreaking work will now be built upon, with a view to finding mechanisms and pathways that could be the target of future therapies.
