Administration of nanodrugs in proper menstrual stage for maximal drug retention in breast cancer.
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.
You
Shaojin
S
Atlanta Research and Educational Foundation, Atlanta VA Medical Center, 1670 Clairmont Road, Decatur, GA 30033, United States. Shaojin.You@va.gov
Li
Wei
W
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000503:physiopathology; D002199:Capillary Permeability; D019454:Chronotherapy; D016503:Drug Delivery Systems; D004971:Estrus / Q000502:physiology; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy / Q000503:physiopathology; D008597:Menstrual Cycle / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D049329:Nanostructures
D000970:Antineoplastic Agents