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Preclinical evaluation of molecular-targeted anticancer agents for radiotherapy
Mechthild Krause1, Daniel Zips, Howard D Thames
1Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Germany.
Abstract:
The combination of molecular-targeted agents with irradiation is a highly promising avenue for cancer research and patient care. Molecular-targeted agents are in themselves not curative in solid tumours, whereas radiotherapy is highly efficient in eradicating tumour stem cells. Recurrences after high-dose radiotherapy are caused by only one or few surviving tumour stem cells. Thus, even if a novel agent has the potential to kill only few tumour stem cells, or if it interferes in mechanisms of radioresistance of tumours, combination with radiotherapy may lead to an important improvement in local tumour control and survival. To evaluate the effects of novel agents combined with radiotherapy, it is therefore necessary to use experimental endpoints which reflect the killing of tumour stem cells, in particular tumour control assays. Such endpoints often do not correlate with volume-based parameters of tumour response such as tumour regression and growth delay. This calls for radiotherapy specific research strategies in the preclinical testing of novel anti-cancer drugs, which in many aspects are different from research approaches for medical oncology.
Insights
Combining molecular-targeted agents with radiotherapy shows promise for cancer treatment. Tumor control assays are crucial for evaluating novel agents targeting cancer stem cells to improve patient survival.
Area of Science:
- Oncology
- Radiation Oncology
- Cancer Therapeutics
Background:
- Molecular-targeted agents alone are not curative for solid tumors.
- Radiotherapy effectively targets and eradicates tumor stem cells.
- Tumor recurrences after radiotherapy are often due to surviving tumor stem cells.
Purpose of the Study:
- To highlight the importance of combining molecular-targeted agents with radiotherapy.
- To emphasize the need for specific experimental endpoints, like tumor control assays, for evaluating novel agents.
- To differentiate preclinical testing strategies for novel anti-cancer drugs in combination with radiotherapy.
Main Methods:
- Utilizing tumor control assays to assess the efficacy of combined treatments.
- Focusing on experimental endpoints that reflect the killing of tumor stem cells.
- Adapting preclinical research strategies for novel anti-cancer drugs when combined with radiotherapy.
Main Results:
- Combination therapy may significantly improve local tumor control and survival.
- Novel agents, even those with modest effects on tumor stem cells, can enhance radiotherapy outcomes.
- Endpoints like tumor regression and growth delay may not accurately reflect the impact on tumor stem cells.
Conclusions:
- Combining molecular-targeted agents with radiotherapy is a promising strategy for improving cancer treatment outcomes.
- Tumor control assays are essential for evaluating the true efficacy of novel agents in combination with radiotherapy.
- Preclinical research for novel anti-cancer drugs requires radiotherapy-specific strategies focusing on tumor stem cell eradication.
