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Mass spectrometry, a new tool for precision medicine

Precision medicine applied to breast cancer has traditionally drawn up patient profiles with the use of techniques such as genomic sequencing and microarrays. Over the past decade, proteomics research has achieved breakthroughs in the identification and quantification of certain biomarkers in clinical samples, which help stratify patients by the sub-type of breast cancer that they develop. Thus, individuals who have these types of tumors can be classified based on the proteomic pattern they present, which helps distinguishing each type of breast cancer based on activities such as metabolism, cell growth, messenger RNA translation or intercellular communication.

These are the conclusions of a recent study published in Nature Communications, containing a detailed description of the “breast cancer maps” derived from the proteomic analyses performed on over forty clinical samples. Though the size of the sample was limited, the work delves into the study of the tumors with greatest incidence, mortality and five-year prevalence in Spanish women, according to data released by the Spanish Medical Oncology Association (SEOM). The article also outlines the clinical applications of proteomics and their importance in future precision medicine.

Source: Tamar Geiger et al., Nature Communications.

But this is not the only study in which proteomics have furthered the state-of-the-art in breast cancer. Another study, led by the molecular oncology department of the Vall d’Hebron Institute of Oncology (VHIO) has shown for the first time that mass spectrometry quantification of therapeutic targets (e.g. HER2) renders a better indicator than the current standard methods used to predict the survival of patients treated with anti-HER2 therapies. “We’ve managed to demonstrate the efficacy of a mass spectrometry platform that makes it possible to isolate and quantify proteins in a reproducible way, and validate its application in breast cancer, which is an intensely-studied form of cancer,” reported VHIO researcher Dr. Paolo G. Nuciforo to Biocores. The SRM-MS (Selected Reaction Monitoring Mass Spectrometry) is more efficient than conventional techniques such as immunohistochemistry or fluorescent in situ hybridization (FISH), according to the work that VHIO scientists published in Molecular Oncology, as these latter technologies are semi-quantitative, have reproducibility problems and do not correctly predict the efficacy of the therapies.

Precision medicine is based on administering therapies that are personalized according to therapeutic targets. At present, breast cancer research has identified HER2, a protein expressed on the surface of tumor cells, as a “target”. However, according to Nuciforo, the levels of HER2 expression are not measured in breast cancer patients. Therefore, the work done at VHIO makes it possible to quantify it and, based on the expression measurement, propose a combination of treatments. “Attempts have been made to apply mass spectrometry in oncology to manage stomach carcinoma, but no predictive value for response to treatment was shown,” states the Vall d’Hebrón researcher. That makes this study the first to provide clear scientific evidence on the clinical usefulness of this technique in oncology.

But the clinical application of mass spectrometry is not limited to cancer research alone. Another example can be found in the group of Dr. Eduard Sabidó, of the Centre for Genomic Regulation in Barcelona, also at work on the translational use of mass spectrometry. His team has focused on comprehending the relevance that mass spectrometry could have on the diagnosis and treatment of patients with multiple sclerosis. “Because of how it enables us to determine mechanisms of action or stratify patients, mass spectrometry, as we understand it, is a powerful tool in clinical and translational research,” states the head of the proteomics unit of the CRG  and Pompeu Fabra University.

Source: Centre for Genomic Regulation

Nonetheless, studies in multiple sclerosis are not as advanced as they are in breast cancer. “It’s our job to lay the groundwork for future hospital practice,” says Sabidó. According to data from Esclerosis Múltiple España, there are 46,000 patients now affected by this neurodegenerative disease in Spain. “It’s a pathology difficult to diagnose, because patients often present symptoms that are similar to those of other neurodegenerative diseases,” states the Centre for Genomic Regulation researcher.

His group, together with the team of Dr. Manuel Comabella (of the Multiple Sclerosis Centre of Catalonia –CEMCAT–and the Clinical Neuroimmunology Unit of the Vall d’Hebron Research Institute–VHIR–) have managed to comprehensively identify a list of 24 proteins that, either because of their known function, or their role in this disease, could have predictive value to improve the diagnosis and establish the prognosis of the pathology over the next 3-5 years. Their goal is to be able to develop an early diagnosis method in the future, and determine the symptoms and molecular biomarkers that could offer reliable clues on the evolution of this pathology. In other words, the use of these tools could facilitate diagnosis in the early stages of multiple sclerosis.

“MALDI is a mass spectrometry technique that had been used in clinical microbiology to identify microorganisms,” says Dr. Francesc Canals in remarks made to Biocores. In the words of the head of the VHIO proteomics laboratory, “Over recent years, techniques have evolved up to a point in which levels of sensitivity have been reached that are good enough to let us analyze items of clinical interest. So in the mid-term, it should be possible to quantify protein markers that are now studied through techniques such as immunohistochemistry, which would in turn allow us to better classify and stratify patients. Mass spectrometry applications in breast cancer or multiple sclerosis are blazing the trail to be followed. According to Canals, this area of research may not have an immediate application now, but it will be keenly relevant for the precision medicine of the future.