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Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
A Review: Genetic Mutations as a Key to Unlocking Drug Resistance in Cervical Cancer
Carla Eksteen1, Johann Riedemann1, Atarah M Rass2
1CancerCare, Cape Gate Oncology Centre, Cape Town, South Africa.
Abstract:
Cervical cancer is the fourth most common cancer in women. Advanced stage and metastatic disease are often associated with poor clinical outcomes. This substantiates the absolute necessity for high-throughput diagnostic and treatment platforms that are patient and tumour specific. Cervical cancer treatment constitutes multimodal intervention. Systemic treatments such as chemotherapy and/or focal radiotherapy are typically applied as neoadjuvant and/or adjuvant strategies. Cisplatin constitutes an integral part of standard cervical cancer treatment approaches. However, despite initial patient response, de novo or delayed/acquired treatment resistance is often reported, and toxicity is of concern. Chemotherapy resistance is associated with major alterations in genomic, metabolomic, epigenetic and proteomic landscapes. This results in imbalanced homeostasis associated with pro-oncogenic and proliferative survival, anti-apoptotic benefits, and enhanced DNA damage repair processes. Although significant developments in cancer diagnoses and treatment have been made over the last two decades, drug resistance remains a major obstacle to overcome.
Insights
Cervical cancer treatment faces challenges with chemotherapy resistance, necessitating personalized platforms. Understanding resistance mechanisms is crucial for developing effective, patient-specific therapies for this common women's cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cervical cancer is a significant global health concern, particularly for women.
- Advanced and metastatic cervical cancer are linked to poor prognoses, highlighting the need for improved therapeutic strategies.
- Current treatments involve multimodal interventions, including chemotherapy and radiotherapy, often utilizing cisplatin.
Purpose of the Study:
- To underscore the critical need for high-throughput, patient- and tumor-specific diagnostic and treatment platforms for cervical cancer.
- To investigate the underlying mechanisms of chemotherapy resistance in cervical cancer.
- To address the limitations of current treatment approaches, particularly cisplatin resistance and toxicity.
Main Methods:
- Review of existing literature on cervical cancer treatment and resistance mechanisms.
- Analysis of genomic, metabolomic, epigenetic, and proteomic alterations associated with chemotherapy resistance.
- Exploration of the physiological consequences of these alterations, including enhanced survival and DNA repair.
Main Results:
- Cisplatin, a cornerstone of cervical cancer therapy, often encounters de novo or acquired resistance.
- Chemotherapy resistance is characterized by complex molecular changes across multiple biological landscapes.
- These alterations promote cancer cell survival, proliferation, and resistance to apoptosis, while enhancing DNA repair capabilities.
Conclusions:
- Drug resistance remains a major impediment in cervical cancer treatment despite advancements in diagnostics and therapeutics.
- Developing patient- and tumor-specific approaches is essential to overcome resistance and improve clinical outcomes.
- Further research into the molecular underpinnings of resistance is vital for designing more effective and less toxic therapies.
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