FGFs to Broadly Protect Chemotherapy-Induced Alopecia

Lu, Ze

Abstract

Chemotherapy-induced alopecia (CIA) is one of the most common and psychologically distressing side effects of cancer chemotherapy. CIA consists of hair loss, reduced hair growth, and structural abnormalities in the newly grown hair. Devastation due to CIA is often severe, and has prompted some patients to refuse chemotherapy. Concern for quality of life issue is gaining importance as the emphasis of cancer treatment is shifting from cure to long-term maintenance. Hence, effective treatment for CIA is needed and timely. No proven treatment for CIA is available. The several agents under development are designed to protect against a single drug or a single drug class and therefore have limited application against combination therapy using two or more drugs with different action mechanisms. The present application is to develop a treatment that can broadly protect against CIA by multiple drugs and drug classes. We have previously found that aFGF combined with bFGF (FGFs) induce up to 10-fold resistance in tumor cells against chemotherapy with multiple chemotherapeutic agents acting by diverse mechanisms. The resistance applies to both the anti-proliferative and apoptotic effects of drugs. Subcutaneous or topical application of FGFs in a neonatal rat model of alopecia reduced the hair loss induced by multiple anticancer drugs (paclitaxel, doxorubicin, cyclophosphamide, cytosine arabinoside), enhanced the subsequent hair growth, and reversed the chemotherapy-induced structural abnormalities in the hair follicles and hair shafts. This result is superior to the effect of published treatments for CIA. Additional preliminary results show that topically applied FGFs (dissolved in DMSO) were localized in hair follicles and the dermis layer and resulted in insignificant systemic absorption. We further found that our first generation liposomal formulation, when applied topically, was localized in hair follicles. Collectively, our preliminary results suggest that liposomal formulations of FGFs for topical administration can selectively protect against CIA without compromising the effectiveness of chemotherapy. The goal of this Phase I application is to develop topical FGF formulations for treating CIA.