Editorial Comment from Dr Miyata and Dr Sakai to Sulfoquinovosylacylpropanediol is a novel potent radiosensitizer in prostate cancer

Abstract

Numerous investigators have evaluated the genetic and molecular characteristics of cancer cells. In addition to cancer cells, the tumor microenvironment is of interest, because it plays a crucial role in cell survival and tumor development. In particular, angiogenic and hypoxic environments are recognized major players in aggressive, malignant cancers. Furthermore, changes in the pathological microenvironment induced by treatment can exert anticancer effects. Thus, understanding the microenvironment at the molecular level is essential to develop treatment strategies in patients with malignancies, including prostate cancer.In the present article, Sawada et al. showed that combined treatment with sulfoquinovosylacylpropanediol (SQAP) and X-ray irradiation remodeled the microenvironment in prostate cancer.1 To understand the interesting findings of this study, knowledge of SQAP is required. SQAP is a sulfoglyco-lipid originally derived from sea urchins expressing α-sulfoquinovosylmonoacylglycerol (SQMG). Unfortunately, the anticancer effects of SQAP are not fully understood. Thus, the authors sought to clarify its pathological function. In contrast, a previous report showed that α-SQMG inhibits DNA polymerase activity, thereby inducing apoptosis. Furthermore, α-SQMG can suppress cell viability in the human gastric cancer cell line, NUGC-3.3 Interestingly, α-SQMG was reported to enhance the radiosensitivity of colon cancer cells through regulation of vascular normalization. 4 These findings formed the basis of the present study.One of the most interesting results of the present study is that the tumor volume in xenograft models using DU-145 and PC3 cells was reduced after combination SQAP administration and radiotherapy. Interestingly, the synergistic tumor growth effect of these therapies was detected in DU145 cells, but not PC3 cells. Likewise, the vascular normalization index, calculated by CD34 and α-smooth muscle actin in DU145-derived tumors, was significantly increased by combined therapy, whereas a significant effect was not detected in PC3-derived tumors. The authors speculated that this difference was caused by innate cellular characteristics. We agree with their opinion; however, further studies are necessary to understand the mechanism of SQAP-induced radiosensitization.In recent years, the importance of radiotherapy in prostate cancer monotherapy and combined therapies has increased. 5 Therefore, as the authors have pointed out, more detailed studies are essential for preclinical examination. For example, the anticancer effects of combined SQAP, radiotherapy and hormonal therapy should be evaluated. However, a xenograft model using subcutaneously implanted human cancer cells in athymic nude mice was utilized in the present study. Therefore, readers should be aware that the effects of the immune system and correlation with a prostate-specific environment are lacking in this study. Studies circumventing these limitations will yield important information regarding this treatment strategy.