FGFs to Broadly Protect Chemotherapy-Induced Alopecia

FGF 可广泛保护化疗引起的脱发

• 批准号: 6935773
• 负责人: ZE LU
• 金额: $ 19.78万
• 依托单位: OPTIMUM THERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-07 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6935773
• 关键词: alopecia; antineoplastics; chemoprevention; dimethylsulfoxide; disease /disorder model; dosage; drug administration rate /duration; drug adverse effect; drug design /synthesis /production; drug screening /evaluation; fibroblast growth factor; hair follicle; laboratory mouse; laboratory rat; liposomes; neoplasm /cancer chemotherapy; nonhuman therapy evaluation; pharmacokinetics; skin disorder chemotherapy; skin pharmacology; topical drug application

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：化学疗法诱导的脱发（CIA）是癌症化学疗法的最常见和心理上令人沮丧的副作用之一。中央情报局包括脱发，头发生长降低以及新成年头发的结构异常。 CIA造成的破坏通常很严重，并促使一些患者拒绝化疗。由于癌症治疗的重点正在从治疗转移到长期维护，因此对生活质量问题的关注变得重要。因此，需要有效的中央情报局治疗。没有可靠的CIA治疗。正在开发的几种药物旨在防止一种药物或单一药物类别，因此使用具有不同动作机制的两种或多种药物对联合治疗的应用有限。目前的应用是开发一种可以通过多种药物和药物类别广泛保护中央情报局的治疗方法。我们以前已经发现，与BFGF（FGFS）结合使用的AFGF在肿瘤细胞中诱导了多达10倍的耐药性，以通过多种化学治疗剂作用于各种机制的化学疗法。该耐药性适用于药物的抗增殖和凋亡作用。 FGF在新生大鼠模型中的皮下或局部应用降低了多种抗癌药物（紫杉醇，阿霉素，环磷酰胺，环磷酰胺，阿拉伯糖苷）诱导的脱发，从而增强了毛发的生长，并增强了化学疗法诱导的结构效果。该结果优于公开的中央情报局治疗方法。其他初步结果表明，局部施加的FGF（溶解在DMSO中）位于毛囊和真皮层中，并导致无关紧要的全身吸收。我们进一步发现，我们的第一代脂质体配方局部应用于毛囊中。总体而言，我们的初步结果表明，局部给药的FGF的脂质体制剂可以选择性地预防CIA，而不会损害化学疗法的有效性。该阶段I应用的目的是开发用于治疗CIA的局部FGF公式。