Frommeyer Timothy C, Rohan Craig A, Spandau Dan F, Kemp Michael G, Wanner Molly A, Tanzi Elizabeth, Travers Jeffrey B
Department of Pharmacology & Toxicology, Boonshoft School of Medicine at Wright State University, Dayton, OH, United States.
Department of Dermatology, Boonshoft School of Medicine at Wright State University, Dayton, OH, United States.
Front Oncol. 2022 Jan 7;11:813132. doi: 10.3389/fonc.2021.813132. eCollection 2021.
The occurrence of non-melanoma skin cancer (NMSC) is closely linked with advanced age and ultraviolet-B (UVB) exposure. More specifically, the development of NMSC is linked to diminished insulin-like growth factor-1 (IGF-1) signaling from senescent dermal fibroblasts in geriatric skin. Consequently, keratinocyte IGF-1 receptor (IGF-1R) remains inactive, resulting in failure to induce appropriate protective responses including DNA repair and cell cycle checkpoint signaling. This allows UVB-induced DNA damage to proliferate unchecked, which increases the likelihood of malignant transformation. NMSC is estimated to occur in 3.3 million individuals annually. The rising incidence results in increased morbidity and significant healthcare costs, which necessitate identification of effective treatment modalities. In this review, we highlight the pathogenesis of NMSC and discuss the potential of novel preventative therapies. In particular, wounding therapies such as dermabrasion, microneedling, chemical peeling, and fractionated laser resurfacing have been shown to restore IGF-1/IGF-1R signaling in geriatric skin and suppress the propagation of UVB-damaged keratinocytes. This wounding response effectively rejuvenates geriatric skin and decreases the incidence of age-associated NMSC.
非黑素瘤皮肤癌(NMSC)的发生与高龄和紫外线B(UVB)暴露密切相关。更具体地说,NMSC的发展与老年皮肤中衰老的真皮成纤维细胞胰岛素样生长因子-1(IGF-1)信号传导减弱有关。因此,角质形成细胞IGF-1受体(IGF-1R)仍处于无活性状态,导致无法诱导包括DNA修复和细胞周期检查点信号传导在内的适当保护反应。这使得UVB诱导的DNA损伤不受控制地增殖,从而增加了恶性转化的可能性。据估计,每年有330万人发生NMSC。发病率的上升导致发病率增加和巨大的医疗成本,这就需要确定有效的治疗方式。在这篇综述中,我们强调了NMSC的发病机制,并讨论了新型预防疗法的潜力。特别是,磨皮、微针、化学剥脱和分次激光换肤等创伤疗法已被证明可以恢复老年皮肤中的IGF-1/IGF-1R信号传导,并抑制UVB损伤的角质形成细胞的增殖。这种创伤反应有效地使老年皮肤恢复活力,并降低与年龄相关的NMSC的发病率。