Dados do Resumo
Título
Platform for personalized therapeutic testing in breast tumors
Introdução
To advance cancer therapies, there is a critical need for models that accurately reflect the complexity of human tumors. To increase the chance of success, it is necessary to undestand the genetic background and make accurate decisions. Patient-derived organoids (PDOs) allow for precision medicine and personalized solutions to the complexity of human tumors proposing ways to translate these models into clinical practice.
Objetivo
By utilizing these matched patient-derived organoids (PDOs), we aim to conduct drug screenings and characterizations that are personalized, practical and cost-effective. Additionally, we propose the potential of these models for real-time precision oncology.
Métodos
Patient tumor samples were originated from our collaborating hospitals. Each sample was divided, and part of the sample was implanted in mice and part was processed to create organoids, for the establishment of a biorepository. We have submitted some of the samples to a 16 treatment protocols used clinically at SUS and to a drug screening of 104 compounds used in target-therapies. Additionally, we have characterized the organoids morphology and molecular profile with their original sample. CAAE: 57006822.8.3002.0068 CEUA-CNPEM:99
Resultados
We have received 98 patient samples from collaborating hospitals and successfully isolated organoids in approximately 60% of cases. Our samples distribution is Luminal A (22%), Luminal B (36%), HER2 amplified (17%), Triple Negative (20%) and unknown (5%). We observed that the organoids maintain the original tumor morphology and retain the expression of receptors and markers. We have submitted all subtypes to the clinically employed protocols and to the target-therapies compounds. In these cases, we observe that organoids respond to protocols accordingly to their subtypes and indicate that some target-therapies compounds might be predictable to use in therapy.
Conclusões
Our findings led to the identification of drugs with significant efficacy against the models. This research might offer valuable methodologies and resources for functional precision medicine and drug development in breast cancer for the first time with Brazilian patients.
Financiador do resumo
Ministério da Saúde NUP 2500.171803/2020-21
Palavras Chave
Organoids; personalized medicine; drug screening
Área
7.Pesquisa básica/translacional
Autores
Guilherme Zweig Rocha, Otto Luiz Dutra Cerqueira, Alex Castro, Renata Spagolla Napoleão Tavares, Alessandra Girasole, Sandra Martha Gomes Dias, Tais vez, Maria José Ferreira Alves, Miyuki Uno, Maria Cristina Rangel, Roger Chammas, Tiago Goss dos Santos, Adriano Beserra, Silvana Soares dos Santos