Related Experiment Video
Updated: Apr 16, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Evaluating the effectiveness of cancer drug sensitization in vitro and in vivo
Mateusz Rytelewski1, Adrian Buensuceso2, Hon S Leong3
1Microbiology and Immunology, Western University.
Abstract:
Due to the high level of heterogeneity and mutations inherent in human cancers, single agent therapies, or combination regimens which target the same pathway, are likely to fail. Emphasis must be placed upon the inhibition of pathways that are responsible for intrinsic and/or adaptive resistance to therapy. An active field of investigation is the development and testing of DNA repair inhibitors that promote the action of, and prevent resistance to, commonly used chemotherapy and radiotherapy. We used a novel protocol to evaluate the effectiveness of BRCA2 inhibition as a means to sensitize tumor cells to the DNA damaging drug cisplatin. Tumor cell metabolism (acidification and respiration) was monitored in real-time for a period of 72 hr to delineate treatment effectiveness on a minute by minute basis. In combination, we performed an assessment of metastatic frequency using a chicken embryo chorioallantoic membrane (CAM) model of extravasation and invasion. This protocol addresses some of the weaknesses of commonly used in vitro and in vivo methods to evaluate novel cancer therapy regimens. It can be used in addition to common methods such as cell proliferation assays, cell death assays, and in vivo murine xenograft studies, to more closely discriminate amongst candidate targets and agents, and select only the most promising candidates for further development.
Insights
Inhibiting BRCA2 sensitizes cancer cells to cisplatin, a DNA-damaging drug. This novel approach, combining metabolic monitoring and metastasis assessment, offers a more effective way to test new cancer therapies.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Therapeutics
Background:
- Cancer's heterogeneity and mutations often lead to treatment failure with single agents or pathway-specific combinations.
- Targeting pathways responsible for intrinsic and adaptive therapy resistance is crucial for effective cancer treatment.
- DNA repair inhibitors are being investigated to enhance chemotherapy and radiotherapy efficacy and prevent resistance.
Purpose of the Study:
- To evaluate BRCA2 inhibition as a strategy to sensitize tumor cells to cisplatin.
- To develop and validate a novel protocol for assessing cancer therapy effectiveness.
Main Methods:
- Real-time monitoring of tumor cell metabolism (acidification and respiration) for 72 hours.
- Assessment of metastatic frequency using a chicken embryo chorioallantoic membrane (CAM) model for extravasation and invasion.
- Utilizing a novel protocol to complement standard assays like proliferation, cell death, and xenograft studies.
Main Results:
- BRCA2 inhibition was evaluated for its potential to sensitize tumor cells to cisplatin.
- The novel protocol provided minute-by-minute insights into treatment effectiveness.
- The CAM model allowed for the assessment of metastatic potential in response to the combined treatment.
Conclusions:
- The developed protocol offers a more refined method for evaluating novel cancer therapy regimens.
- This approach can help discriminate between candidate targets and agents, selecting the most promising for further development.
- Combining BRCA2 inhibition with cisplatin shows potential for overcoming treatment resistance.
