Study reveals factors in metabolism that can enhance efficiency of treatment for gynecologic tumors

The findings, published in Gynecologic Oncology, pave the way to the development of a blood test that can be performed by a physician at the time of diagnosis to help personalize treatment.

By Thais Szegö  |  Agência FAPESP – Blood plasma from women with ovarian and uterine cancer can contain molecules that suggest whether they will respond well to chemotherapy or suffer a relapse, according to a study conducted by researchers in the Department of Gynecology at the Federal University of São Paulo’s Medical School (EPM-UNIFESP) in Brazil, in partnership with colleagues at the University of California Irvine (UCI) in the United States. 

The study sample consisted of 50 women with ovarian and endometrial tumors who were submitted to surgery and first-line chemotherapy. The findings are published in Gynecologic Oncology.

“Our aim was to measure the metabolic signatures – molecules originating in the metabolism and present in the bloodstream – that could be associated with a specific illness or condition,” said physician Paulo D’Amora, a member of the steering committee of EPM-UNIFESP’s Molecular Gynecology and Metabolomics Laboratory, and holder of a scholarship from FAPESP’s Young Investigator Program.

In this case, he explained, the study involved analyzing important compound classes such as the amino acids valine and phenylalanine (linked to immunity), and lipids such as the acylcarnitines, lysophosphatidylcholines and sphingomyelins (associated with alterations that lead to stimulation of inflammatory pathways and energy expenditure).

The analysis was performed by mass spectrometry, a technique widely used by clinical laboratories worldwide to identify and quantify substances in biological samples. 

“With the aid of a next-generation mass spectrometry system, we measured the ions emitted by the compounds of interest in the plasma samples collected from the patients,” D’Amora said. “Ions are accelerated and fragmented in the spectrometer. Each metabolite has a specific fragmentation pattern, a unique identity.” 

The results pointed to the patients who were platinum-sensitive or platinum-resistant. Chemotherapy against these gynecologic tumors typically involves drugs that contain platinum. 

The participants were divided into two groups: 38 platinum-sensitive patients (83% of the total), and eight platinum-resistant patients (17%). The spectrometry results were correlated with those of clinical and laboratory exams and, after a metabolomic analysis, led to information on the patients’ clinical response, such as disease-free survival, time to progression and overall survival.

The researchers began with these types of tumor because they are sensitive to chemotherapy with platinum-based drugs. They were able to identify patients with metabolic profiles associated with the best clinical response and prognosis, or with unfavorable profiles and a poor prognosis. This information enables physicians to personalize treatment, enhancing its efficiency and the probability of a cure. 

The results point to a future in which oncologists will use a blood test performed in the clinic to discover the patient’s metabolic signature and use it to help decide on the best way to manage the case. 

“We’re working on ways of ensuring that the biomarkers and algorithms found in the study can achieve the validation levels required by regulators in Brazil and abroad so as to win accreditation for their use in laboratory medicine and clinical pathology. Once that happens, they can be used in clinical practice,” said D’Amora, who in 2016 and 2017 won Scholar-in-Training Awards from the American Association for Cancer Research (AACR). 

The article “Platinum resistance in gynecologic malignancies: Response, disease free and overall survival are predicted by biochemical signature: A metabolomic analysis” is at: www.sciencedirect.com/science/article/pii/S0090825821006466?via%3Dihub.