Oncology Forum - Conference Reports

Conference Report

New Approaches to Radiation Therapy

C N Coleman
National Cancer Institute
USA

Dr Coleman described radiation as 'focused biology' in that it is now possible to induce biological perturbations to the tumour by focusing the radiation dose. The dose and dose- rate may be adjusted and radiation can be administered systemically via radio-labelled antibodies. Very low doses of radiation can induce changes in gene expression indicating that there are numerous molecular targets for radiation therapy. The cellular response differs according to the tissue and tumour type. Using 1 Gy for a small amount of tumour cell killing (30%), a large number of different molecular lesions are created and the aim for this millennium is to learn how to modulate these molecular processes.

Table 1. Novel targets for radiation oncology

Target	Action
Tumour macro-environment surrounding healthy tissues	Thiol-based radioprotector Alteration of cytokine cascade
Tumour micro-environment	Hypoxia, pH, glucose Cellular stress response Angiogenesis
DNA damage (halopyrimidines), recognition (Ku, ATM), repair enzymes, checkpoints (p53, abrogate G2)
Signal transduction anywhere along the pathway	Receptor/ligand (bFGF, EGFR) Signal transduction pathway (MAP, kinase, Ras, Rai)
Apoptosis	Induction Balance pro-/anti-apoptotic processes NFkB
Protein degradation	Proteosome
Gene therapy HRE, RRE, p53

The classic target for radiation oncology is to increase DNA damage to increase cell killing. However, the new paradigm is to use non-DNA targets such as signal transduction pathways, kinase phosphatases, DNA repair enzymes, and transcriptional apparatus, to alter the cells' homeostasis (table 1).

One of the best mechanisms for discovering novel radiation targets is based on genetic diseases because of the associated defects in DNA damage repair. Non-mammalian systems and new classes of anti-cancer drugs are of interest from a radiation viewpoint. "As we study more and more of the molecular lesions in diseases, we will be able to elucidate novel targets for radiation therapy", suggested Dr Coleman.

In Summary

Novel radiation therapy approaches for the next decade include intensity modulated radiotherapy, real-time imaging and real-time dosimetry in technical physics, while in biological physics, molecular dosimetry, imaging biological processes, and isotope-tagged molecules will be important. In biology, there is an interest in molecular alterations by radiotherapy and by the tumour/healthy tissue environment as potential targets for normal tissue protection and radiation sensitisation, as well as the epigenetic effects. Clinically, it is important to optimise combined modality therapy including the best technical radiotherapy and application of combined molecular approaches such as novel molecular treatments and non-DNA targets.