Newly developed strategies for improving sensitivity to radiation by targeting signal pathways in cancer therapy

Abstract

Inherent and acquired resistance of cancer cells is increasingly recognized as a significant impediment to effective radiation cancer treatment. As important intracellular factors, aberrant tumor transmembrane signal transduction pathways, which include the prosurvival cascades (PI3K ⁄ Akt, MAPK ⁄ ERK and JAK ⁄ STAT) and the proapoptosis pathways (Wnt, p53 and TNF-a ⁄ NF-jB), have been proved to be crucial determinants of the probability of cell sensitivity to radiation in malignant lesions. There is increasing evidence that targeting the abnormal pathways that can regulate the activity of the DNA damage response and further influence the response of tumor cells to radiation may be suitable for improving radiation sensitization. Preclinical and clinical evidence suggest that agents targeting aberrant tumor signals can effectively improve the therapeutic effect of ionizing radiation. Therefore, in this review, we discuss the intricate interplay between tumor responses to radiation with the aberrant signal pathways, and the potential druggable targets within the pathways to sensitize tumors without significant collateral damage to normal tissues. The application of novel targeting compounds to manipulate the aberrant signal of tumor cells in clinical treatments is also addressed. (Cancer Sci 2013; 104: 1401-1410 I onizing radiation (IR) is an inalienable part of modern cancer management given the unique advantages of being noninvasive and devoid of intense systemic toxicity. As an integral component of adjuvant treatment strategies for primary tumors and palliative treatment strategies for advanced and metastatic tumors, more than 50% of diagnosed cancer patients receive radiation therapy (RT; alone or combination with chemotherapy or surgery) worldwide. However, RT offers various degrees of success; there is still an increased recurrence and treatment failure in patients. Retrospective studies show that extracellular factors, such as location, size and hypoxia, play important roles in the lack of response to radiotherapy.(1,2) In recent 15 years, as important intracellular factors, the signaling pathways that can regulate the activity of the DNA damage response, cell growth, differentiation and development have been proved to undergo oncogenic changes far more than other molecule groups.(3-5) The genetic alterations that are activated by the signal cascades in premalignant cells and further characterize neoplasm genomes have also been highlighted. (6)(7)(8) Preclinical and clinical studies have indicated that the aberrant signal pathways in cancer cells are crucial determinants of the probability of the improvement of sensitivity to radiation in malignant lesions (9)(10)(11)(12)(13) ; and a more nuanced understanding of the complex radiobiology mechanisms for the response of tumors to RT has paved the way for exploring novel or combinatorial therapeutic approaches for cancer treatment using IR. Hence, the targeted agents that can specifically inhibit the activity of the signal cascades could abrogate the radiores...

Capsaicin: A novel radio-sensitizing agent for prostate cancer

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The Enhancement of Radiation Sensitivity in Nasopharyngeal Carcinoma Cells via Activation of the Rac1/NADPH Signaling Pathway

“…Efforts are ongoing to improve the efficacy of radiotherapy, and increasing the level of radiosensitivity has shown to be an effective therapeutic strategy, particularly for nasopharyngeal carcinoma. To enhance sensitivity to radiation and reduce the side effects, it is necessary to find new radiosensitizing agents (17). We previously reported that 1,8-dihydroxy-3-acetyl-6-methyl-9, 10 anthraquinone (GXHSWAQ-1), synthesized according to the basic structure of emodin, exhibited a 1.46-fold radiosensitization of nasopharyngeal carcinoma CNE-1 cells (18,19).…”

Crosstalk between long non‐coding RNAs and Wnt/β‐catenin signalling in cancer

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