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Updated: Sep 30, 2025
Heterotypic Three-dimensional In Vitro Modeling of Stromal-Epithelial Interactions During Ovarian Cancer Initiation and Progression
Published on: August 28, 2012
Developing Clinically Relevant Acquired Chemoresistance Models in Epithelial Ovarian Cancer Cell Lines
Priti S Shenoy1,2, Sourav Chakraborty1,2, Snehal M Gaikwad3
1Imaging Cell Signalling & Therapeutics Lab, Advanced Centre for Treatment, Research and Education in Cancer, TMC, Navi Mumbai, 410210, India.
Abstract:
Chemoresistance, the ability of cancer cells to overcome therapeutic interventions, is an area of active research. Studies on intrinsic and acquired chemoresistance have partly succeeded in elucidating some of the molecular mechanisms in this elusive phenomenon. Hence, drug-resistant cellular models are routinely developed and used to mimic the clinical scenario in-vitro. In an attempt to identify the underlying molecular mechanisms that allow ovarian cancer cells to gradually acquire chemoresistance, we have developed isogenic cellular models of cisplatin and paclitaxel resistance (singularly and in combination) over six months, using a clinically relevant modified pulse method. These models serve as important tools to investigate the underlying molecular players, modulation in genetics, epigenetics, and relevant signaling pathways, as well as to understand the role of drug detoxification and drug influx-efflux pathways in development of resistance. These models can also be used as screening tools for new therapeutic molecules. Additionally, repurposing therapeutic agents approved for diseases other than cancer have gained significant attention in improving cancer therapy. To investigate the effect of metformin on acquirement of chemoresistance, we have also developed a combinatorial model of metformin and platinum-taxol, using two different strategies. All these models were subsequently used to study modulation in receptor tyrosine kinase pathways, cancer stem cell functionalities, autophagy, metastasis, metabolic signatures, and various biological processes during development of chemoresistance. Herein, we outline the protocols used for developing these intricate resistant cellular models.
Insights
Researchers developed ovarian cancer cell models resistant to chemotherapy drugs like cisplatin and paclitaxel. These models help study chemoresistance mechanisms and test new therapies, including metformin combinations.
Area of Science:
- Oncology
- Cancer Biology
- Drug Resistance Research
Background:
- Chemoresistance is a major challenge in cancer therapy, limiting treatment efficacy.
- Understanding the molecular basis of chemoresistance is crucial for developing effective strategies.
- Existing in vitro models are essential for studying drug resistance mechanisms.
Purpose of the Study:
- To develop isogenic cellular models of ovarian cancer exhibiting resistance to cisplatin and paclitaxel.
- To investigate the molecular mechanisms underlying acquired chemoresistance in ovarian cancer.
- To explore the role of metformin in combination with chemotherapy in overcoming chemoresistance.
Main Methods:
- Development of isogenic ovarian cancer cell models with acquired resistance to cisplatin and paclitaxel over six months using a modified pulse method.
- Creation of combinatorial models involving metformin and platinum-taxol using two distinct strategies.
- Utilizing these models to analyze modulations in receptor tyrosine kinase pathways, cancer stem cell functions, autophagy, metastasis, and metabolic signatures.
Main Results:
- Established robust cellular models mimicking clinical chemoresistance in ovarian cancer.
- These models facilitate the investigation of genetic, epigenetic, and signaling pathway alterations during resistance development.
- The models allow for the study of drug efflux/influx mechanisms and their role in chemoresistance.
Conclusions:
- The developed isogenic cellular models are valuable tools for elucidating chemoresistance mechanisms in ovarian cancer.
- These models can be employed for screening novel therapeutic agents and repurposed drugs like metformin.
- Further research using these models will advance our understanding of ovarian cancer drug resistance and inform treatment strategies.
