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Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents
Brigette B Y Ma1, Robert G Bristow, John Kim
1Department of Medical Oncology and Hematology, Precess Margaret Hospital, University Health Network, Suite 5-210, 610 University Ave, Toronto, Ontario, Canada M5G 2M9.
Purpose:
Molecular targeted agents have been combined with radiotherapy (RT) in recent clinical trials in an effort to optimize the therapeutic index of RT. The appeal of this strategy lies in their potential target specificity and clinically acceptable toxicity.
Design:
This article integrates the salient, published research findings into the underlying molecular mechanisms, preclinical efficacy, and clinical applicability of combining RT with molecular targeted agents. These agents include inhibitors of intracellular signal transduction molecules, modulators of apoptosis, inhibitors of cell cycle checkpoints control, antiangiogenic agents, and cyclo-oxygenase-2 inhibitors.
Results:
Molecular targeted agents can have direct effects on the cytoprotective and cytotoxic pathways implicated in the cellular response to ionizing radiation (IR). These pathways involve cellular proliferation, DNA repair, cell cycle progression, nuclear transcription, tumor angiogenesis, and prostanoid-associated inflammation. These pathways can also converge to alter RT-induced apoptosis, terminal growth arrest, and reproductive cell death. Pharmacologic modulation of these pathways may potentially enhance tumor response to RT though inhibition of tumor repopulation, improvement of tumor oxygenation, redistribution during the cell cycle, and alteration of intrinsic tumor radiosensitivity.
Conclusion:
Combining RT and molecular targeted agents is a rational approach in the treatment of solid tumors. Translation of this approach from promising preclinical data to clinical trials is actively underway.
Insights
Combining radiotherapy (RT) with molecular targeted agents shows promise for optimizing cancer treatment. This approach targets specific molecular pathways to enhance tumor response and improve therapeutic outcomes in clinical trials.
Area of Science:
- Oncology
- Radiation Oncology
- Molecular Biology
Background:
- Radiotherapy (RT) is a cornerstone of cancer treatment.
- Molecular targeted agents offer specificity and manageable toxicity.
- Combining RT with targeted agents aims to improve the therapeutic index.
Purpose of the Study:
- To review the molecular mechanisms, preclinical efficacy, and clinical applications of combining RT with molecular targeted agents.
- To explore the potential of this combination strategy in optimizing cancer therapy.
Main Methods:
- Integration of published research findings on molecular targeted agents and RT.
- Focus on agents targeting signal transduction, apoptosis, cell cycle checkpoints, angiogenesis, and cyclo-oxygenase-2.
- Analysis of preclinical and clinical data.
Main Results:
- Molecular targeted agents directly impact cellular responses to ionizing radiation (IR).
- These agents modulate pathways including proliferation, DNA repair, cell cycle, transcription, angiogenesis, and inflammation.
- Potential to enhance RT efficacy through improved tumor oxygenation, cell cycle redistribution, and altered radiosensitivity.
Conclusions:
- The combination of RT and molecular targeted agents is a rational strategy for solid tumor treatment.
- Promising preclinical data supports ongoing clinical trials for this therapeutic approach.