Non-Targeted Radiation Effects in Radiotherapy &Roles of Radiation-Induced Genomic Instability and of the Bystander Effect in Cancer Cure by Radiotherapy

Abstract

Local tumour control by radiotherapy requires the complete sterilization of all tumour 'stem' cells in the tumour volume. Neither bystander effect nor radiation-induced genomic instability is able to contribute substantially to the probability of local tumour control of the primary cancer by radiotherapy. However, the progeny of these surviving tumour 'stem' cells are likely to suffer from radiation-induced genomic instability, which results in the persistent appearance of non-stem cells, i.e. a reduced probability of self-maintenance. This results in a slower growth rate of the recurrent tumour, a reduced stem-cell fraction and, as a consequence, an increased radiosensitivity of the recurrent tumour. In some recurrent tumours, particularly those that develop very late and grow very slowly, radiosensitivity may be further increased by increased intrinsic radiosensitivity, which could be related to the as yet poorly de ned phenotype of 'small colony formation'.

Mathematical modelling of radiotherapy strategies for early breast cancer

“…Furthermore, it is known that genomic instability arises in tumours both spontaneously and as a result of treatment with radiotherapy (Yang et al, 1989;Sarkaria et al, 1995;Durante et al, 1996;Colley-Durel et al, 2001;Lorimore et al, 2001;Trott, 2001;Goldberg, 2003;Roychoudhuri et al, 2004;Tozeren et al, 2005). As we have presented a partial differential equation continuum model, we cannot explicitly incorporate the fact that random genomic instabilities arise in single, individual cells.…”

Tumour Stem Cells&The Evidence and the Ambiguity

“…If not explained by small stem cell fractions, radiation effects beyond the stochastic dose-dependent cell inactivation have to be invoked, such as the bystander effect, heritable radiation damage, or the massive tissue necrosis and vascular breakdown seen after curative doses. Yet there is no sound experimental evidence to support this speculative interpretation (14).…”

Abscopal effect in a patient with chronic lymphocytic leukemia during radiation therapy: a case report

“…Radiotherapy to one cell has direct impact on an adjacent cell resulting in bystander effect [ 13 , 14 ]. There have been two main theories proposed to explain the abscopal antitumor effect.…”