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Programmed cell death and radioresistance
R E Meyn1, L C Stephens, L Milas
1Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
Whereas apoptosis is a critical mode of cell deletion in normal organism development, apoptotic cells are also observed in tumors, especially following cytotoxic treatments, leading to questions about their role in tumor response to therapy. We have conducted a series of studies using murine tumor models and found that the ability of the tumor cells to undergo apoptosis correlates with tumor response to radiation. The best correlation was with the pretreatment apoptotic index, suggesting that apoptosis in some tumors may govern radiocurability by regulating the number of tumor clonogens. However, other roles for apoptosis in tumor response to radiation have not been ruled out. One of the important observations that has come from this work has been the heterogeneity in apoptosis propensity both within the cell population of a given tumor and among different types of tumors. Such findings underscore the fact that apoptosis is under complex genetic control and that some of the same oncogenes and tumor suppressor genes that are responsible for tumor initiation and progression to malignancy also dictate the apoptotic response to treatment. Understanding the biochemical and molecular pathways that govern this process may ultimately allow the development of strategies for modulating apoptosis for therapeutic benefit.
Insights
Tumor cell apoptosis, or programmed cell death, is crucial for radiation therapy effectiveness. Pretreatment apoptosis levels in tumors predict how well they respond to radiation, highlighting its role in cancer treatment.
Area of Science:
- Oncology
- Cell Biology
- Radiation Biology
Background:
- Apoptosis (programmed cell death) is vital for development and observed in tumors post-treatment.
- The role of apoptosis in tumor response to therapy remains an area of investigation.
Purpose of the Study:
- To investigate the correlation between tumor cell apoptosis and response to radiation therapy.
- To explore the heterogeneity of apoptosis propensity in tumors and its genetic underpinnings.
Main Methods:
- Studies utilizing murine tumor models.
- Assessment of tumor cell apoptosis and correlation with radiation response.
Main Results:
- Tumor cell apoptosis propensity correlates with radiation response in murine models.
- Pretreatment apoptotic index showed the strongest correlation with radiocurability.
- Significant heterogeneity in apoptosis propensity was observed within and among different tumor types.
Conclusions:
- Apoptosis may govern tumor radiocurability by regulating clonogen number.
- Apoptosis is under complex genetic control, involving oncogenes and tumor suppressor genes.
- Understanding apoptosis pathways could lead to therapeutic strategies for modulating treatment response.