Currently, fairly powerful imaging techniques can spot tumors and metastases. But tumor cells could be detected much earlier and laboratories have started looking for circulating biomarkers in order to improve patient care. Two recent studies have identified biomarkers of interest.
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A biomarker is a precisely measurable characteristic used as an indicator of a body function, disease or drug action. As a result, research is evolving on the identification of biomarkers, particularly for cancers. This is the case, for example, of small or long non-coding RNAs – there are not only genes coding for proteins in our genome – which are more expressed in certain cancers.
Biomarkers are very numerous and give different biological indications. Some could indicate the presence of cancer, others warn of the risk of developing metastasis, and still others predict patients’ response to treatment. Two studies aimed to identify specific biomarkers of breast cancer, in order to adapt the treatment of patients as early as possible.
A biomarker in preventing the risk of developing secondary cancer
The first study identified miR-662, a microRNA that could predict at a very early stage the formation of bone metastases in breast cancer patients, more than 10 years in advance. Indeed, this biomarker is associated with bone metastases. “ It plays a role in the nesting of cancer cells within the bone marrow to form a micrometastasis, before the metastasis stage which can be detected clinically years later », Explains to Futura the co-author of the study Philippe Clézardin, Inserm research director and professor of bone oncology at the University of Sheffield.
The study published in the British Journal of Cancer aimed in particular to quantify the microRNAs circulating in the blood of patients from the moment of diagnosis of breast cancer or just after tumor surgery and to follow them for approximately ten years. “ We can predict the risk of metastatic relapse at 5 years with the biomarker miR-662, but it is not a marker of metastases either.specifies the professor. A correlation is made between the quantity at the time of the surgical procedure and the occurrence over time of relapse. » As metastases are multifactorial, miR-662 is not the only factor at play.
In total, the researchers looked at the expression of more than 2,500 different microRNAs before focusing on miR-662. If the level of the latter is high in a patient’s blood, then her relative risk of developing a bone metastasis is two to three times higher than a patient with a low level. “ There is a high risk that the patient already has micrometastases in the bone marrow. Indeed, the blood sample is taken after surgery, so the blood analysis cannot come from the primary tumor and the expression of a factor becomes very interesting. »
If the clinical study is still at the experimental stage, other clinical cohorts will be needed to ensure that this microRNA is a valid biomarker. but he’s heading in the right direction » according to the researcher.
A second biomarker to predict patients’ response to treatment
Published in the journal EMBO Mol Med, the second study this time identified an enzyme making it possible to predict the response of patients with breast cancer to tamoxifen (Tam), a standard anti-estrogen treatment for these cancers. So-called “luminal” breast cancer can be treated with Tam, but 25% of patients relapse due to resistance to treatment. However, there is currently no biomarker predictive of sensitivity to Tam.
Still with the aim of finding the best treatment as early as possible, the study identified PMRT5 as a biomarker of interest. It is co-directed by Dr Muriel Le Romancer, Inserm research director, and Dr Olivier Trédan, oncologist at the Lyon Cancer Research Center. “ When this protein is located in the nucleus of cells, it will participate in the effect of Tam, which is to inhibit the action of the estrogen receptor, explains Muriel Le Romancer. We suggest looking at the diagnosis of the expression of this protein with a score. If the score is high enough, this means that it is present in the right place, in the nucleus, and we know that the patient will respond to Tam. Whereas if we are below the score, the protein is more in the cytoplasm and the patient will have little chance of responding to treatment. »
This result can be explained by the fact that the estrogen receptor is located in the nucleus. This is a prerequisite for the action of Tam in the nucleus: a certain quantity of this enzyme is required in the nucleus for a certain number of tumor cells to be regulated by Tam.
Ultimately, “ the idea would be to combine antiestrogen treatments with a drug that promotes PRMT5 localization in the nucleus to ensure a response to tamoxifen in all premenopausal patients », concludes the researcher.
