Differential Expression of NOTCH-1 and Its Molecular Targets in Response to Metronomic Followed by Conventional Therapy in a Patient with Advanced Triple-Negative Breast Cancer

Alice Ilari; Viola Cogliati; Noorhan Sherif; Emanuela Grassilli; Daniele Ramazzotti; Nicoletta Cordani; Giorgio Cazzaniga; Camillo Di Bella; Marialuisa Lavitrano; Marina Elena Cazzaniga; Maria Grazia Cerrito

doi:10.3390/biomedicines12020272

Differential Expression of NOTCH-1 and Its Molecular Targets in Response to Metronomic Followed by Conventional Therapy in a Patient with Advanced Triple-Negative Breast Cancer

Biomedicines. 2024 Jan 25;12(2):272. doi: 10.3390/biomedicines12020272.

Affiliations

¹ School of Medicine and Surgery, Milano-Bicocca University, 20900 Monza, Italy.
² Phase 1 Research Centre, Fondazione IRCCS San Gerardo dei Tintori, Via Pergolesi 33, 20900 Monza, Italy.
³ Department of Pathology, Fondazione IRCCS San Gerardo dei Tintori, Via Pergolesi 33, 20900 Monza, Italy.

Abstract

A group of 27 patients diagnosed with metastatic triple-negative breast cancer (mTNBC) was randomly distributed into two groups and underwent different lines of metronomic treatment (mCHT). The former group (N 14) received first-line mCHT and showed a higher overall survival rate than the second group (N 13), which underwent second-line mCHT. Analysis of one patient still alive from the first group, diagnosed with mTNBC in 2019, showed a complete metabolic response (CMR) after a composite approach implicating first-line mCHT followed by second-line epirubicin and third-line nab-paclitaxel, and was chosen for subsequent molecular characterization. We found altered expression in the cancer stemness-associated gene NOTCH-1 and its corresponding protein. Additionally, we found changes in the expression of oncogenes, such as MYC and AKT, along with their respective proteins. Overall, our data suggest that a first-line treatment with mCHT followed by MTD might be effective by negatively regulating stemness traits usually associated with the emergence of drug resistance.

Keywords: AKT; NOTCH-1; c-MYC; cancer stem cells (CSCs); metastatic triple-negative breast cancer (mTNBC); metronomic therapy (mCHT).

Grants and funding

This research was supported by the H2020-co-funded project Instand-NGS4P (grant agreement No. 874719 to M.L.), and by the Fondazione Umberto Veronesi (FUV postdoc fellowship award in 2023 to V.C.) and by Centro Studi Raffaella Trabattoni.