Healthy cells can only divide a limited number of times during an organism's lifetime.

In contrast, tumour cells are immortal: they proliferate indefinitely and uncontrollably, and this is the defining characteristic of cancer.

Researchers from the Telomeres and Telomerase Group at the CNIO (Spanish National Cancer Research Center), led by Maria Blasco, have studied for the first time the possibility of treating lung cancer by targeting the telomeres, the structures that protect the ends of chromosomes and whose condition determines the cell's ability to divide indefinitely.

The results, as explained by the researchers in the journal Cell Death & Differentiation, show that, indeed, targeting telomeres "might be an effective therapeutic strategy" against non-small cell lung cancer, which is responsible for much of the mortality in lung cancer patients.

The work has Sergio Piñeiro as first author, recipient of a postdoctoral contract from the Spanish Association Against Cancer (AECC).

 "Removing immortality from cancer cells is a therapeutic strategy that has not yet been exploited in the fight against cancer," says Maria Blasco.

Focus on the tumour microenvironment

Lung cancer is one of the leading causes of cancer death.

The long-term ineffectiveness of current therapies and late diagnosis mean that only one in five patients survive more than five years.

Specifically, non-small cell lung cancer is responsible for 85% of lung cancer-associated deaths.

The work now published focuses on the so-called tumour microenvironment, which is a set of cells and factors surrounding the tumour that plays a crucial role in the development of cancer and the response to therapies.

The researchers analysed the impact of dysfunctional telomeres.

Also, they studied the effect of telomerase deficiency on the cellular microenvironment of non-small cell lung tumours, telomerase being the enzyme that repairs telomeres.

Telomerase deficiency

Telomeres are protein structures located at the ends of chromosomes.

At each cell division, telomeres shorten until, after a certain number of divisions, the shortening becomes excessive and the cell stops dividing.

This happens in healthy cells, but not in most tumour cells.

Telomerase expression is reactivated in 90% of human tumours.

Because of the action of telomerase, the telomeres in tumour cells maintain a minimum functional length, which allows them to divide indefinitely.

CNIO researchers studied what happened when they caused a telomerase deficit in the lung tumour microenvironment.

They also deliberately damaged their telomeres, using the compound 6-thio-dG.

"It is the first time that the involvement of telomerase and dysfunctional telomeres in the lung tumour microenvironment has been investigated," explains Sergio Piñeiro, currently at the Spanish National Research Council (CSIC) in La Rioja.

Damaged telomeres hold back the tumour

Telomerase deficiency and dysfunctional telomeres slowed tumour progression.

The researchers observed a reduction in tumour implantation and vascularisation in the lung, while increasing the vulnerability of tumours to DNA damage and cell death.

Tumour cell proliferation and inflammation were also decreased, and the anti-tumour response of the immune system was enhanced.

As the authors write in Cell Death & Differentiation, "we address by the first time the implication of TERT [telomerse] and dysfunctional telomeres in the lung tumour microenvironment. Our results demonstrate that targeting telomeres might be an effective therapeutic strategy in non-small cell lung cancer".

Source: Centro Nacional de Investigaciones Oncológicas (CNIO)