Predictors of Treatment Response in Low-Grade Serous Ovarian Cancer Cell Lines
| Thursday, August 14, 2025 |
| 10:30 AM - 10:37 AM |
| Ballroom 2 and 3 |
Overview
Dr Seema Kumari
Speaker
Dr Seema Kumari
Phd Candidate
Westmead Institute for Medical Research
Predictors of Treatment Response in Low-Grade Serous Ovarian Cancer Cell Lines
Abstract
BACKGROUND: Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of ovarian cancer with distinctive genomic characteristics and low response to platinum chemotherapy. Outcomes for advanced LGSOC are poor with limited treatment options, therefore effective and tailored treatment options need to be explored. We aimed to better understand molecular features associated with response to non-platinum chemotherapy, and to the MEK-inhibitor, trametinib in well-defined LGSOC cell line models.
METHODS: Cell viability was assessed following docetaxel, paclitaxel, gemcitabine, pegylated liposomal doxorubicin (PLD) and trametinib exposure in eight LGSOC cell lines (CellTiter 96™ MTS Assay, Promega). RNA was extracted, sequenced (RNAseq, Illumina HiSeq2000) and analysed using EdgeR & clusterProfiler.
RESULTS: The LGSOC cell lines had MAPK pathway variants that are reflective of clinical samples (Table 1). MPSC1, HCC5075 and HOC7 were relatively sensitive to all agents. Gene set variation analysis highlighted a cell cycle signature in these lines and they all had a doubling time of < 24 hours, potentially underlying treatment sensitivity.
AOCS2 and HO433 were the least responsive to trametinib, as might be expected since they lack RAS/RAF alterations. Interestingly, HO433 demonstrated extreme resistance to docetaxel, paclitaxel and PLD, while being highly sensitive to gemcitabine. Differential gene expression showed that ABCB1 was uniquely overexpressed in HO433 (average log2 CPM= 7.03; Table 1) compared with the other LGSOC cell lines. ABCB1 encodes P-glycoprotein, a transmembrane transporter that plays a role in the efflux of various drugs, and over-expression is well-known mechanism of multidrug resistance.
CONCLUSIONS: Transcriptomic analysis identified genes and pathways associated with treatment response in patient-derived LGSOC cell lines. A higher proliferation rate may contribute to chemosensitivity, while ABCB1 overexpression may underlie multidrug resistance in HO433. Further mechanistic studies in cell lines and validation in patient samples are required.
METHODS: Cell viability was assessed following docetaxel, paclitaxel, gemcitabine, pegylated liposomal doxorubicin (PLD) and trametinib exposure in eight LGSOC cell lines (CellTiter 96™ MTS Assay, Promega). RNA was extracted, sequenced (RNAseq, Illumina HiSeq2000) and analysed using EdgeR & clusterProfiler.
RESULTS: The LGSOC cell lines had MAPK pathway variants that are reflective of clinical samples (Table 1). MPSC1, HCC5075 and HOC7 were relatively sensitive to all agents. Gene set variation analysis highlighted a cell cycle signature in these lines and they all had a doubling time of < 24 hours, potentially underlying treatment sensitivity.
AOCS2 and HO433 were the least responsive to trametinib, as might be expected since they lack RAS/RAF alterations. Interestingly, HO433 demonstrated extreme resistance to docetaxel, paclitaxel and PLD, while being highly sensitive to gemcitabine. Differential gene expression showed that ABCB1 was uniquely overexpressed in HO433 (average log2 CPM= 7.03; Table 1) compared with the other LGSOC cell lines. ABCB1 encodes P-glycoprotein, a transmembrane transporter that plays a role in the efflux of various drugs, and over-expression is well-known mechanism of multidrug resistance.
CONCLUSIONS: Transcriptomic analysis identified genes and pathways associated with treatment response in patient-derived LGSOC cell lines. A higher proliferation rate may contribute to chemosensitivity, while ABCB1 overexpression may underlie multidrug resistance in HO433. Further mechanistic studies in cell lines and validation in patient samples are required.
Biography
I am a medical oncologist, and a PhD student passionate about personalised cancer care. The focus of my PhD is on identifying biomarkers predictive of treatment response in patients with low grade serous ovarian cancer.
Session Chair
Tim Clay
St John Of God Subiaco Hospital
