The effects of metronomic chemotherapy on ovarian cancer

Background: Ovarian cancer is the fifth leading cause of cancer-related mortality among women. Current treatments, which include paclitaxel and platinum-based therapies, achieve complete remission in 75% of patients. However, this remission is often short-lived, leading to recurrence and death due to metastatic spread. Recent studies from our laboratory and others have identified ovarian cancer cells that exhibit characteristics of cancer stem cells (CSCs) and are resistant to chemotherapy. Consequently, standard chemotherapeutic approaches do not cure the disease and instead promote chemoresistance through the emergence of this CSC-like phenotype.

Our pioneering research and clinical observations suggest that metronomic chemotherapy (MET)-the administration of conventional chemotherapy (cisplatin) in low, minimally toxic doses at frequent intervals—has the potential to maintain therapeutic efficacy while minimising the toxic effects of chemotherapy on normal cells, particularly immune cells. This project aims to investigate the effects of MET on ovarian cancer cells, especially regarding therapeutic resistance, by utilising both in vitro and in vivo models. Additionally, we will examine the impact of MET on the function and phenotype of various immune cells (including CD8+ T cells, CD4+ T cells, NK cells, NKT cells, MAIT cells, Tregs, etc.) isolated from normal human blood and from patients treated with MET therapy.

Project aims:

1. To determine and compare the effects of standard doses and MET doses of chemotherapy (cisplatin) on patient-derived ovarian cancer cell lines and/or tumour cells isolated from the ascites of ovarian cancer patients using in vitro assays, global proteomics, and in vivo models.

2. To assess and compare the impact of standard doses and MET doses of chemotherapy on the function and phenotype of immune cells isolated from normal blood and from the blood of ovarian cancer patients treated with both standard and MET doses of chemotherapy.
Methods: Tissue culture of cell lines and tumour cells isolated from ovarian cancer patients, flow cytometry, Western blot, quantitative real-time PCR (qRT-PCR), immunohistochemistry, immunofluorescence, global proteomics, and animal studies.

Ethics Approvals: Human and animal ethics approval for this project has been obtained.