Current chemotherapy of cancer typically employs combinations of powerful anti-neoplastic agents. Most therapeutic combinations include anti-neoplastic agents that cause loss of scalp hair (chemotherapy-induced alopecia). Particularly, frequently used alopecia-inducing anti-neoplastic agents are cyclophosphamide, adriamycin, etoposide, taxol and vincristine. Alopecia is clearly the most feared side effect of chemotherapy. Patients have been known to refuse chemotherapy treatment because of it, and it seems not unreasonable to suspect that the psychological devastation resulting from this treatment-related hair loss may impact therapy success. To date, no elective preventive treatment is available to patients. Induction of a conserved protective response, the so-called stress protein response, was shown by many laboratories to protect various types of cultured cells against killing by essentially all classes of anti-neoplastic agents currently in clinical use. The present proposal will test in animal models the hypothesis that prior localized induction of the stress protein response in mitotically active cells of (scalp) hair follicles will protect these cells against killing by cyclophosphamide, adriamycin, etoposide, taxol and vincristine, resulting in the prevention of alopecia. Localization of the induction of the stress protein response will ensure that the preventive treatment will not interfere with the cytotoxic activity of the anti-neoplastic agents in cells other than those of hair follicles, i.e., that the preventive treatment of alopecia will not diminish chemotherapy efficacy.
| Jimenez, Joaquin J; Roberts, Stephen M; Mejia, Jessica et al. (2008) Prevention of chemotherapy-induced alopecia in rodent models. Cell Stress Chaperones 13:31-8 |
