You Shaojin, Li Wei
Atlanta Research and Educational Foundation, Atlanta VA Medical Center, 1670 Clairmont Road, Decatur, GA 30033, United States.
Med Hypotheses. 2008;71(1):141-7. doi: 10.1016/j.mehy.2007.12.018. Epub 2008 Mar 4.
Recent advances in cancer therapy have utilized nanovectors to deliver cytotoxic drugs (so called nanodrugs) to reduce the drug related side effects and improve anti-cancer efficiency. Cancer tissues consist of inherent leaky blood vessels with high permeability, which allows enhanced permeation and retention of therapeutic nanodrugs (EPR effect). The periodical sex hormonal milieus during menstrual cycle regulate the cyclic expression of VEGF in breast cancer and modulate the cancer vascular permeability. Since the expression of cancer VEGF varies considerablely great at different menstrual cycle stages, it is conceivable that the variation between the highest and lowest cancer vascular permeabilities during menstrual cycle is significant. We hypothesize that nanodrugs (i.e. Caelyx and/or Abraxane) given at the proper menstrual stage with predicted highest VEGF expression and cancer vascular permeability allow significantly increased drug retention in breast cancer, and subsequently result in the maximal cancer growth control and minimal cancer metastatic spread. On contrary, if the nanodrugs are given at the menstrual stage with predicted lowest VEGF expression and cancer vascular permeability, the drug retention within the cancer will be substantial low. This hypothesis can be tested via prospective and/or retrospective clinical trial studies on premenopausal patients or via a syngeneic mouse mammary tumor line and female mouse model.
癌症治疗的最新进展利用纳米载体递送细胞毒性药物(即所谓的纳米药物),以减少药物相关的副作用并提高抗癌效率。癌组织由具有高渗透性的固有渗漏血管组成,这使得治疗性纳米药物能够增强渗透和滞留(EPR效应)。月经周期中的周期性性激素环境调节乳腺癌中VEGF的周期性表达,并调节癌血管通透性。由于癌组织VEGF的表达在不同月经周期阶段差异很大,可以想象月经周期中癌血管通透性的最高值与最低值之间的差异是显著的。我们假设,在预测VEGF表达和癌血管通透性最高的适当月经阶段给予纳米药物(即凯素和/或白蛋白结合型紫杉醇),可使乳腺癌中的药物滞留显著增加,进而实现最大程度的癌症生长控制和最小程度的癌症转移扩散。相反,如果在预测VEGF表达和癌血管通透性最低的月经阶段给予纳米药物,癌症内的药物滞留将非常低。这一假设可以通过对绝经前患者进行前瞻性和/或回顾性临床试验研究,或通过同基因小鼠乳腺肿瘤系和雌性小鼠模型来验证。