br Amino acid usage in cancer br Perspective

Amino Cilostazol usage in cancer
Perspective High glucose consumption is a common feature of several types of tumor cells. Therefore, so far, in vivo positron emission tomography (PET) imaging with the glucose analog 18F-fluorodeoxyglucose (18F-FDG) has been used to detect various tumors. However, it has not been used for brain tumors because of high background. As discussed above, glutamine dependency is also a common feature of tumors but not for normal cells. Venneti et al. [174], successfully detected gliomas by in vivo PET imaging using the glutamine analog 4-18F-(2S,4R)-fluoroglutamine with low background. Small numbers of biologically different tumor cells with stem-like properties, such as self-renewal and tumor-initiating ability, have been detected in various tumors including head and neck cancers [175], [176], [177], [178], [179], [180]. These cells, called cancer stem cells (CSCs), are less proliferative than other cancer cells and are insensitive to chemotherapy and radiotherapy. CSCs play important roles in both local recurrence and distant metastasis. CD44 variant 9 (CD44v) is a nearly universal CSC marker in various tumor types [181]. CD44v stabilizes the cysteine transporter xCT (see Fig. 6), whereas sulfasalazine inhibits xCT activity, resulting in tumor suppression by decreasing glutathione formation and increasing oxidative stress [182], [183], [184]. The anticancer activity of sulfasalazine is food pyramid likely due to its targeting of CSCs, especially preventing local recurrence and metastasis. Clinical trials of sulfasalazine have yielded successful results in patients with gastric cancer, ulcerative colitis-related cancers and urogenital cancer [182], [183], [185]. Despite difficulties in developing a new drug targeting CSCs, the combination of sulfasalazine with conventional chemotherapy agents has been reported to selectively inhibit CSCs [186]. Although targeting CSCs may prevent local recurrence and distant metastasis, non-CSCs may acquire the properties of CSCs epigenetically, thereby complicating treatment [186]. Controlling the mechanisms underlying reprogramming should be determined to prevent non-CSCs from the de novo acquisition of CSC properties, with efforts concentrated on epigenetic regulatory networks for the development and/or stabilization of cancer stemness. Further studies are expected to develop new and selective CSC-targeting agents with high efficacy.
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