Abstract
Much has been investigated to improve the beneficial effects of radiotherapy especially in that case where radioresistant behavior is observed. Beyond simple identification of resistant phenotype the discovery and development of specific molecular targets have demonstrated therapeutic potential in cancer treatment including radiotherapy. Alterations on transduction signaling pathway related with MAPK cascade are the main axis in cancer cellular proliferation even as cell migration and invasiveness in irradiated tumor cell lines; then, for that reason, more studies are in course focusing on, among others, DNA damage enhancement, apoptosis stimulation, and growth factors receptor blockages, showing promising in vitro results highlighting molecular targets associated with ionizing radiation as a new radiotherapy strategy to improve clinical outcome. In this review we discuss some of the main molecular targets related with tumor cell proliferation and migration as well as their potential contributions to radiation oncology improvements.
Highlights
To achieve a better understanding of the different targeted cancer responsiveness a wide range of experimental tumors of various histologic types have been developed for radiobiological studies [1] whose effects, induced by ionizing radiation (IR), can be investigated through many approaches, allowing the identification of radioresistance or radiosensitivity of human cancer cell lines [2]
When the antiangiogenesis drug Endostar combined with radiotherapy was applied on A549 cells, increased radiation sensitivity by transcriptional factors expression reduction of TGF-β1 and hypoxiainducible factor- (HIF-)1α was noticed [72], and it was observed in human colon adenocarcinoma cell line WiDr surviving after radiation therapy by acquiring HIF-1 activity and translocation towards tumor blood vessels in a dependent cellular dynamics after irradiation recurrence, what might suggest basis for targeting HIF-1 after radiation therapy [73, 74], especially in hypoxic tumors
Recent studies showed that miR-193a-3p was able to radiosensitize both U251 and HeLa cells by accumulation of intracellular reactive oxygen species increasing DNA damage and apoptosis directly targeting the antiapoptotic Mcl-1 gene [99], while silencing miR-21 in radioresistant non-small cell lung cancer (NSCLC) A549 cells sensitized them to IR by inhibiting cell proliferation and enhancing cell apoptosis through inhibition of phosphatidylinositol 3kinase (PI3K)/Akt signaling pathway [100]
Summary
To achieve a better understanding of the different targeted cancer responsiveness a wide range of experimental tumors of various histologic types have been developed for radiobiological studies [1] whose effects, induced by ionizing radiation (IR), can be investigated through many approaches, allowing the identification of radioresistance or radiosensitivity of human cancer cell lines [2]. In colon cancer cells IR increases the expression of ST6Gal I, which, in turn, is involved in radioresistance and radiation-induced migration via sialylation of integrin β1 that may be a novel target for overcoming radiationinduced survival, especially adhesion and migration of this kind of tumor [7, 8] The understanding and identification of specific molecular targets with significant therapeutic implications in order to develop new strategies for radiotherapy are crucial to improve patient survival without substantially increasing toxicity
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