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Chemoresistance in Ovarian Cancer: Prospects for New Drugs
Shivani Tendulkar1, Suneel Dodamani1
1Dr. Prabhakar Kore Basic Science Research Center, KLE Academy of Higher Education and Research, Nehru Nagar, Belagavi- 590010, Karnataka, India.
Abstract:
This review focuses on the conventional treatment, signaling pathways and various reasons for drug resistance with an understanding of novel methods that can lead to effective therapies. Ovarian cancer is amongst the most common gynecological and lethal cancers in women affecting different age groups (20-60). The survival rate is limited to 5 years due to diagnosis in subsequent stages with a reoccurrence of tumor and resistance to chemotherapeutic therapy. The recent clinical trials use the combinatorial treatment of carboplatin and paclitaxel on ovarian cancer after the cytoreduction of the tumor. Predominantly, patients are responsive initially to therapy and later develop metastases due to drug resistance. Chemotherapy also leads to drug resistance causing enormous variations at the cellular level. Multifaceted mechanisms like drug resistance are associated with a number of genes and signaling pathways that process the proliferation of cells. Reasons for resistance include epithelial-mesenchyme, DNA repair activation, autophagy, drug efflux, pathway activation, and so on. Determining the routes on the molecular mechanism that target chemoresistance pathways are necessary for controlling the treatment and understanding efficient drug targets can open light on improving therapeutic outcomes. The most common drug used for ovarian cancer is Cisplatin that activates various chemoresistance pathways, ultimately causing drug resistance. There have been substantial improvements in understanding the mechanisms of cisplatin resistance or chemo sensitizing cisplatin for effective treatment. Therefore, using therapies that involve a combination of phytochemical or novel drug delivery system would be a novel treatment for cancer. Phytochemicals are plant-derived compounds that exhibit anti-cancer, anti-oxidative, anti-inflammatory properties and reduce side effects exerted by chemotherapeutics.
Insights
Ovarian cancer drug resistance limits survival. Novel therapies combining phytochemicals or advanced drug delivery systems show promise for overcoming chemoresistance and improving patient outcomes.
Area of Science:
- Gynecologic Oncology
- Cancer Pharmacology
- Molecular Biology
Background:
- Ovarian cancer is a lethal gynecologic malignancy with poor 5-year survival rates, often due to late-stage diagnosis and tumor recurrence.
- Conventional treatments like cisplatin, carboplatin, and paclitaxel face significant challenges from acquired chemoresistance.
- Drug resistance in ovarian cancer involves complex cellular mechanisms, including epithelial-mesenchymal transition, DNA repair, autophagy, and drug efflux pumps.
Purpose of the Study:
- To review conventional ovarian cancer treatments, drug resistance mechanisms, and explore novel therapeutic strategies.
- To understand the molecular pathways underlying chemoresistance, particularly cisplatin resistance.
- To identify potential targets for improving therapeutic efficacy and patient outcomes in ovarian cancer.
Main Methods:
- Literature review of conventional treatments, signaling pathways, and drug resistance mechanisms in ovarian cancer.
- Analysis of molecular mechanisms contributing to chemotherapy resistance, including genetic and cellular variations.
- Exploration of novel therapeutic approaches, such as phytochemicals and advanced drug delivery systems.
Main Results:
- Chemotherapy, while initially effective, often leads to drug resistance and metastases in ovarian cancer patients.
- Multiple molecular pathways, including epithelial-mesenchymal transition and DNA repair, are implicated in chemoresistance.
- Cisplatin, a common chemotherapeutic, activates various resistance pathways, necessitating strategies to overcome its resistance.
Conclusions:
- Targeting molecular mechanisms of chemoresistance is crucial for effective ovarian cancer treatment.
- Combinatorial therapies involving phytochemicals or novel drug delivery systems represent promising avenues for overcoming drug resistance.
- Further research into chemoresistance pathways and novel agents can significantly improve therapeutic outcomes for ovarian cancer patients.
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