I read in the study entitled ( Radiation-Induced Reprogramming of Breast Cancer Cells conducted by that CHANN LAGADEC, ERINA VLASHI, LORENZA DELLA DONNA, CARMEN DEKMEZIAN, FRANK PAJONK) ,The detailed understanding of the underlying pathways could lead to novel combination therapies that will potentially enhance the efficacy of radiation treatment . My question : How effective is it ? Are there any other suggestions ?
I hope to provide us with references , thanks.
Cancer stem cells (CSCs) play an important role in disease recurrence after radiation treatment as a result of intrinsic properties such as high DNA repair capability and antioxidative capacity. It is unclear, however, how CSCs further adapt to escape the toxicity of the repeated irradiation regimens used in clinical practice. Here, Saya H et al. have exposed a population of murine glioma stem cells (GSCs) to fractionated radiation in order to investigate the associated adaptive changes, with the ultimate goal of identifying a targetable factor that regulates acquired radioresistance. They have shown that fractionated radiation induces an increase in IGF1 secretion and a gradual upregulation of the IGF type 1 receptor (IGF1R) in GSCs. Interestingly, IGF1R upregulation exerts a dual radioprotective effect. In the resting state, continuous IGF1 stimulation ultimately induces downregulation of Akt/extracellular-signal-regulated kinases (ERK) and FoxO3a activation, which results in slower proliferation and enhanced self-renewal. In contrast, after acute radiation, the abundance of IGF1R and increased secretion of IGF1 promote a rapid shift from a latent state toward activation of Akt survival signaling, protecting GSCs from radiation toxicity. Treatment of tumors formed by the radioresistant GSCs with an IGF1R inhibitor resulted in a marked increase in radiosensitivity, suggesting that blockade of IGF1R signaling is an effective strategy to reverse radioresistance. Together, our results show that GSCs evade the damage of repeated radiation not only through innate properties but also through gradual inducement of resistance pathways and identify the dynamic regulation of GSCs by IGF1R signaling as a novel mechanism of adaptive radioprotection.
(Ref; Stem Cells. 2013 Apr;31(4):627-40. doi: 10.1002/stem.1328. IGF1 receptor signaling regulates adaptive radioprotection in glioma stem cells.)
Regarding the comment of Go J Joshida, the response and involved pathways should largely depend on the type of cancer or the tissue of their origin, gliomas being still a major challenge. Generally CSCs, very much like their normal counterparts, are considered to be highly resistant to radiation and also chemotherapy. This is at least to a large extent because of their extremely low proliferation rate and high expression of multiple drug transporters/detoxification. To my knowledge a promising strategy is to get first rid of the major tumor load (by surgery) and then to activate the CSCs to make them more sensitive towards treatment ( for example see papers by A Trumpp).
A brief general answer. Radiation treatment might be effective but not selective. Therefore, benefits might be less than the hazardous effects on non-target cells. I see working on genes related to PCD is a very good strategy if we are able to provoke genes triggering PCD in the target cancerous cells, only. Excuse me. This is an answer of non-specialist in the field.
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