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Metabolic agents may increase efficacy of gynecological oncology treatments

Metabolic agents may increase efficacy of gynecological oncology treatments

In the blood of women with ovarian and endometrial tumors, researchers from the Department of Gynecology at the Escola Paulista de Medicina of the Federal University of São Paulo (EPM-Unifesp), in partnership with specialists from the University of California, Irvine, in the United States, found factors that may indicate Patients are more likely to respond well to treatment or relapse.

To reach this conclusion, they analyzed the plasma of 50 women with ovarian and endometrial cancer who had undergone first-line surgery and chemotherapy. The search results were reveal in the magazine Gynecological Oncology.

“Our goal was to measure what are called metabolic fingerprints, that is, metabolic molecules present in the bloodstream that may be associated with a specific disease or condition,” the doctor explains. Paulo Damora, member of the Board of Directors of the Laboratory of Molecular and Metabolic Gynecology in the Department of Gynecology at EPM-Unifesp and FAPESP Young Investigator Fellow in the Emerging Centers Program (São Paulo State Research Support Foundation), who funded part of the study.

As the scientist explains, some important classes of compounds have been analyzed, such as the amino acids valine and phenylalanine (related to immunity) and lipids such as acylcarnitine, lysophosphatidylcholine and sphingomyelin (associated with changes that lead to the stimulation of inflammatory pathways and energy expenditure).

This process was carried out using a technology called mass spectrometry, which allows the identification and quantification of substances in biological samples, and is widely used in clinical laboratories around the world.

“With the help of a state-of-the-art mass spectrometry system, we measure ions released from compounds of interest found in patients’ plasma samples. These ions are accelerated and divided within the spectrometer and each important metabolite has a specific fragmentation pattern – a unique identity,” explains D’Amora. The results showed that the participants were sensitive and those resistant to platinum, a substance widely used in chemotherapy against these gynecological cancers.

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Participants were divided into two groups: one of the platinum-sensitive patients, consisting of 38 individuals (83% of the sample), and the other of the platinum-resistant patients, consisting of eight individuals (17%). These results were associated with clinical and laboratory data and, after biostatistical analysis (analysis of the group of metabolites in the sample), led to information about the clinical response of these patients, such as disease-free survival, and time to disease progression in general. Survival.

The research, performed so far with these types of tumors because they are sensitive to the chemotherapeutic agent evaluated, has allowed the identification of patients with metabolic profiles associated with better clinical response and good prognosis and those with an unfavorable profile and a worse prognosis regarding disease progression. With this information on hand, clinicians can perform a more individualized treatment, with significant improvement in efficiency and treatment opportunities.

The findings point to a future in which oncologists will be able to use a blood test performed at the time of diagnosis to aid decision making while managing the condition.

“We are working to bring the biomarkers and algorithms discovered in the study to the satisfactory levels of verification required by national and international accreditation bodies in laboratory medicine and clinical pathology, so that we can soon be able to use them in clinical practice,” says D’Amora.

Article Platinum resistance in gynecological malignancies: response, disease-free, and overall survival predicted by a biochemical signature: a metabolic analysis. It can be read at: https://doi.org/10.1016/j.ygyno.2021.08.001.