Biofilm Chemoprevention of Head/Neck Skin Cancer

描述（由申请人提供）： 在临床上，非黑色素瘤皮肤癌（NMSC）是最常见的恶性肿瘤之一，在美国每年有超过90万新发病例。头部/颈部皮肤似乎只占身体表面积的不到10%。然而，由于更多的阳光照射，70%至80%的NMSC发生在这个区域。目前，NMSC治疗推荐手术切除，但创伤大，术后复发和并发症多，费用高。NMSC的发育是一个缓慢的过程，因此化学预防将是一个有前途的策略。局部应用化学预防药物有望保持治疗效果，并且副作用比全身方案少。不幸的是，目前的战略，短期局部绘画，提供非常有限的好处。聚合物制成的粘附膜（PAF）由于其临床安全性、可控的药物释放和优异的粘附性而在镇痛剂、抗生素或其他药物的局部应用中获得了多年的成功。我们最近的动物研究表明，局部应用PAF进行癌症化学预防是安全有效的。我们的研究也表明塞来昔布对这种治疗的有效性。在这项拟议的研究中，我们将（1）测试局部组织对PAF递送的塞来昔布局部治疗的反应，并优化小鼠模型正常皮肤中的塞来昔布剂量;和（2）确定PAF-Celecoxib贴剂是否有效且安全地用于局部预防相同小鼠模型中紫外线诱导的NMSC。这种局部PAF-塞来昔布化学预防NMSC，如果在这项拟议的研究中成功，将提供一个新的预防皮肤癌的策略。它将是目前手术切除或其他局部治疗的理想替代方案。我们认为，它将比目前的方法更有效，产生更少的副作用。此外，这种疗法将是安全和方便的，足以让患者在家里自我管理，以同样的方式，他们通常适用于一块商业“创可贴”表。同样的概念也适用于位于口腔、宫颈或其他组织表面的癌前病变。这是首次将聚合物生物膜技术用于头颈部NMSC化学预防的研究。我们相信，一项成功的研究将使患者受益匪浅。

DESCRIPTION (provided by applicant): Clinically, non-melanoma skin cancer (NMSC) is one of the most common malignancies, with more than 900,000 new cases per year in the United States. The Head/neck skin seems only to account for less than 10% of the body's surface area. However, 70 to 80% of NMSCs occur in this region, due to greater sun exposure. Currently, surgical excision is recommended for NMSC treatment, but with significant trauma, postoperative recurrence and complications, and cost. NMSC development is a slow process so that chemoprevention would be a promising strategy. Topical application of chemopreventives is expected to preserve treatment effect and have fewer side effects than a systemic regime. Unfortunately, current strategies, with short-term topical painting, provide very limited benefit. Polymer-made adhesive film (PAF) has been successful for many years in the topical application of analgesics, antibiotics or other medications to tissues, due to its clinical safety, controllable drug release and excellent adherence. Our recent animal studies show that topical PAF application for cancer chemoprevention is safe and effective. Our studies also indicate effectiveness of Celecoxib for such treatment. In this proposed study, we will (1) test local tissue response to topical treatment of PAF-delivered Celecoxib, and optimize Celecoxib dose in normal skin of a mouse model; and (2) determine whether the PAF-Celecoxib patch is effective and safe for topical prevention of UV-induced NMSCs in the same mouse model. This topical PAF-Celecoxib chemoprevention of NMSCs, if successful in this proposed study, will offer a new preventive strategy for skin cancers. It would be an ideal alternative to current surgical excision or other localized treatments. We believe that it will be more effective and produce fewer side effects than current approaches. Furthermore, this therapy will be safe and convenient enough for patients to self-administer at home in the same way as they usually apply a piece of commercial "band-aid" sheet. The same concept will also be applicable to premalignant lesions located on oral, cervical or other tissue surfaces. This is the first study to use polymer biofilm technique for NMSC chemoprevention on head/neck region. We believe that a successful study will greatly benefit patients.