Imaging and mass spectrometry-based metabolomics applied to the study of drug resistance in neoadjuvant therapy for breast cancer: the search for a predictive test

• Grant number: 19/04314-6
• Support Opportunities: Regular Research Grants
• Duration: August 01, 2019 - July 31, 2022
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Andréia de Melo Porcari
• Grantee: Andréia de Melo Porcari
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil
• Associated researchers: Lívia Schiavinato Eberlin ; Sophie Françoise Mauricette Derchain
• Associated scholarship(s): 20/01941-7 - Training in handling biological samples and approaching patients to collect Biobank., BP.TT

Abstract

Breast cancer is a heterogeneous disease that encompass different histological types and molecular subtypes, and it is the main cancer type among women. One of the histological types, the ductal one, accounts for ~80% of the cases, and it is basically classified in luminal and non-luminal subtypes. Neoadjuvant chemotherapy is usually employed as treatment in these cases, aiming the reduction of the tumor area and damages caused by tumor's removal. Nonetheless, ~50% of the women submitted to this treatment do not respond to the neoadjuvant treatment. The investigation over global metabolic alterations among cancer cells that are sensitive and resistant to chemotherapy is still needed and, such a research may result in a predictive test grounded in mass spectrometry-based metabolomics which could predict patient outcome to chemotherapy before her/his exposure to such an undesired treatment, resulting in a personalized medicine strategy aiming at the use of plasma tests, with clear potential for clinical practice. This project aims at characterizing the metabolome of chemotherapy-resistant and -sensitive patients based on two approaches: (i) tumor tissue and tumor bed tissue from patients classified as good and bad responders and (ii) serum of patients before and after their exposure to neoadjuvant chemotherapy. We aim at deepening the knowledge of biochemical pathways that take place in the resistance mechanisms. Our ultimate objective is to find biomarkers, accessible through serum analysis, that could indicate which patients will be benefited from the neoadjuvant chemotherapy and which will not. Moreover, we aim at the metabolic characterization of the different molecular subtypes of ductal breast cancer, and we will try to understand the effects of drug resistance in these different subtypes. This project corroborates with the investments of São Francisco University that made possible to set up and equip a new multi-users laboratory for mass spectrometry and to hire the proponent of this project. We could also establish partnerships with the women's hospital CAISM - UNICAMP and with the University of Texas, thus allowing the appropriate collection of samples and the clinical and technological backgrounds needed to achieve unique results. (AU)

Scientific publications

(9)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MORAIS, ESTEFENSON MARQUES; ROSINI SILVA, ALEX AP; ARAUJO DE SOUSA, FRANCISCO WDERSON; BARBOZA DE AZEVEDO, IZABELLE MARIA; SILVA, HELANE FRANCA; GONCALVES SANTOS, ALICE MARIA; AGUIAR BESERRA JUNIOR, JOSE EVANDO; DE CARVALHO, CAROLINE PAIS; EBERLIN, MARCOS NOGUEIRA; PORCARI, ANDREIA M.; et al. Endophytic Trichoderma strains isolated from forest species of the Cerrado-Caatinga ecotone are potential biocontrol agents against crop pathogenic fungi. PLoS One, v. 17, n. 4, p. 19-pg., 2022-01-01. (19/04314-6)

LICE, IZABELLA; SANCHES, JOSE MARCOS; CORREIA-SILVA, REBECA D.; CORREA, MAB P.; ICIMOTO, MARCELO Y.; SILVA, ALEX A. R.; SANCHEZ-VINCES, SALVADOR; PORCARI, ANDREIA M.; MOREIRA, VANESSA; GIL, CRISTIANE D.. ffects of Formyl Peptide Receptor Agonists Ac9-12 and WKYMV in In Vivo and In Vitro Acute Inflammatory Experimental Model. CELLS, v. 11, n. 2, JAN 2022. (19/15017-2, 20/03565-2, 19/04314-6)

DE OLIVEIRA, ALEXANDRE CAVENATTI; DAVANCO, MARCELO GOMES; DE CAMPOS, DANIEL ROSSI; GODOY SANCHES, PEDRO HENRIQUE; GONCALVES CIRINO, JOAO PEDRO; CARVALHO, PATRICIA DE OLIVEIRA; ANTONIO, MARCIA APARECIDA; COELHO, EDVALDO CAPOBIANGO; PORCARI, ANDREIA M.. Sensitive LC-MS/MS method for quantification of rivaroxaban in plasma: Application to pharmacokinetic studies. BIOMEDICAL CHROMATOGRAPHY, v. 35, n. 9, SEP 2021. (19/04314-6)

SANCHES, PEDRO H. G.; DE OLIVEIRA, DANILO C.; DOS REIS, IVAN G. M.; FERNANDES, ANNA M. A. P.; SILVA, ALEX A. R.; EBERLIN, MARCOS N.; CARVALHO, PATRICIA O.; DUARTE, GUSTAVO H. B.; PORCARI, ANDREIA M.. Fitting Structure-Data Files (.SDF) Libraries to Progenesis QI Identification Searches. Journal of the Brazilian Chemical Society, v. N/A, p. 7-pg., 2023-02-03. (18/13317-6, 19/04314-6)

CARDOSO, MARCELLA R.; SILVA, ALEX AP ROSINI; TALARICO, MARIA CECILIA R.; SANCHES, PEDRO H. GODOY; SFORCA, MAURICIO L.; ROCCO, SILVANA A.; REZENDE, LUCIANA M.; QUINTERO, MELISSA; COSTA, TASSIA B. B. C.; VIANA, LAIS R.; et al. Metabolomics by NMR Combined with Machine Learning to Predict Neoadjuvant Chemotherapy Response for Breast Cancer. CANCERS, v. 14, n. 20, p. 16-pg., 2022-10-01. (18/24069-3, 19/04314-6)

PELOSI, ANDREA; FERNANDES, ANNA MARIA A. P. C.; MACIEL, LEONARDO; SILVA, ALEX A. R.; MENDES, GIULIA F.; BUENO, LUISA F. G.; SILVA, LIVIA MARIA F. M.; BREDARIOL, RAFAEL G.; SANTANA, MAYCON; PORCARI, ANDREIA; et al. Liquid chromatography coupled to high-resolution mass spectrometry metabolomics: A useful tool for investigating tumor secretome based on a three-dimensional co-culture model. PLoS One, v. 17, n. 9, p. 8-pg., 2022-09-21. (19/04314-6, 18/21471-5, 19/23592-7, 18/21906-1)

ROSINI SILVA, ALEX AP.; CARDOSO, MARCELLA R.; REZENDE, LUCIANA MONTES; LIN, JOHN Q.; GUIMARAES, FERNANDO; PAIVA SILVA, GEISILENE R.; MURGU, MICHAEL; PRIOLLI, DENISE GONCALVES; EBERLIN, MARCOS N.; TATA, ALESSANDRA; et al. Multiplatform Investigation of Plasma and Tissue Lipid Signatures of Breast Cancer Using Mass Spectrometry Tools. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 10, MAY 2020. (16/07822-4, 19/04314-6)

GARZA, KYANA Y.; SILVA, ALEX AP ROSINI; ROSA, JONAS R.; KEATING, MICHAEL F.; POVILAITIS, SYDNEY C.; SPRADLIN, MEREDITH; SANCHES, PEDRO H. GODOY; MOURA, ALEXANDRE VARAO; GUTIERREZ, JUNIER MARRERO; LIN, JOHN Q.; et al. Rapid Screening of COVID-19 Directly from Clinical Nasopharyngeal Swabs Using the MasSpec Pen. Analytical Chemistry, v. 93, n. 37, p. 12582-12593, SEP 21 2021. (19/04314-6)

SANCHES, PEDRO H. G.; SILVA, ALEX A. R.; PORCARI, ANDREIA M.. Plasma lipid profiles differ among chronic inflammatory diseases. EBIOMEDICINE, v. 70, p. 2-pg., 2021-08-11. (19/04314-6)