Dados do Trabalho

Name: Next Frontiers to Cure Cancer
Start: 2023-09-15
End: 2023-09-16
Location: Expo Center Norte (Pavilhão Amarelo)

Título

High-Throughput Screening Identifying Histone Modification Drugs to Manage Mucoepidermoid Carcinoma

Introdução

Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignant tumor, presenting a 5-year disease-free survival of 76%. The current treatment for MEC is surgical excision, and the development of highly effective systemic strategies for MEC remains a challenge. In particular, there are few effective targeted therapies for MEC. Recently, we have shown that epigenetic events play an important role in MEC behavior. We have also shown that drugs that target epigenetic modifications provide encouraging results. In this way, high-throughput (HT) screening platforms have facilitated the rapid testing of many drugs.

Objetivo

To present an HT drug screening by histone modification drugs (HMD) to pharmacologically assessed MEC and improve therapies.

Métodos

High-precision-liquid-handler was used to seed UM-HMC3a cells and to administer drugs in a HT-format. MEC pharmacological assessment was conducted using a 2D-bulk tumor, and 3D-cancer stem cells (CSC) models. Cell death was evaluated by propidium iodide in adherent cells and tumorspheres (CSC). ALDH levels and clonogenic potential were also investigated. All data were evaluated using ImageXpress from molecular devices.

Resultados

We identified 81 compounds inducing cell death in bulk MEC and 92 compounds in CSC MEC. From this first HT screening, the top-drug candidates targeting each cell subpopulation was selected. After a careful validation process, we identified the final 4 compounds able to disrupt MEC. Additionally, ALDH levels were significantly reduced just for drugs selected based on CSC, while the clonogenic potential was reduced after the treatment with all selected drugs.