The kinome pathways in radioresistance breast cancer stem cells

Abstract

Radiotherapy (RT) has been considered as a key part in treatment of breast cancer patients, and is an obligatory for those undergo conservative surgery which could decrease the local recurrence rate. However, for those patients who still relapse, the exact mechanism behind radioresistance is still largely unrevealed. In this current article, Guo et al. and his colleges have been developed an approach for profiling the global kinome to give better understanding of the expression pattern of the human kinases in cells and tissues (1).RT is the using of ionizing radiations for treatment many types of cancers. There are different sources of ionizing radiations, radioactive isotopes which used as local site or systematically. On the other hand, there is another type which used external beam RT that used high energy of X-ray, in this type the radiation doses are subdivided into different small dosage for several weeks and this is to allow the normal tissues to recover after sub-lethal radiation damage between treatments. Despite of the significantly reduction of the recurrence after a wide local excision (WLE) for localized ductal carcinoma in situ (DCIS) and to early invasive cancers and RT to axilla in node-positive invasive cancers, there are patients who have relapse with unknown reasons (2-5).One of the newly reason for the radioresistance is the presence of tumor rescuing units also known as cancer stem like cells in enriched form which play an important role in resistance to multiple therapy including radiation, to support this concept many researches have been conducted on the cancer cells and they found that cancer stem cells are repopulated after radiation treatment and get more resistance to radiations than non-stem cells and this is the failure of the therapy (1,6,7). On the other hand, the exact molecular mechanism underlying the radioresistance is still unclear.From this point, researchers have been found that the radioresistance is made by prosurvival genes induced by signaling pathways including protein kinases and transcription factors (8,9).Identifying the most important kinases in radioresistance cancer cells will help us to narrow our focusing on specific target and development the appropriate therapies.To unveil the most significant kinome pathways which are associated with radioresistance breast cancers, Guo et al. in this paper (1) used MCF7/C6 a radioresistance clone and MCF7/WT to quantify the entire kinome in both type of cells and he constructed a MRM library with selected peptides and more than 300 unique kinases and applying LC-MRM coupled with isotope-coded desthiobiotinconjugated ATP-affinity probes to quantify the entire kinome in this cell line as they had done. In brief, he used probes with three components: enrichment moiety, linker and binding moiety for labeling cell lysates and followed by schedule LC-MRM which produces high specificity, sensitivity, reproducibility than other approaches. As a result, he was able to identify and quantify in current paper 120 kinases and he found on...