Weir Sydney A, Kc Kailash, Shoaib Shoaib, Yusuf Nabiha
Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
School of Medicine, Alabama College of Osteopathic Medicine, Dothan, AL 36303, USA.
Life (Basel). 2023 Jun 1;13(6):1310. doi: 10.3390/life13061310.
Interferons (IFNs) have demonstrated therapeutic potential in various skin cancers, specifically squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma. The precise mechanism through which type I IFNs exert their antitumor effects in skin cancers is still being studied. However, intralesional type I IFN can be used as an alternative to surgery for select patient populations, and high-dose systemic IFN therapy has been shown to be promising in patients with operable high-risk or metastatic melanoma. Despite the therapeutic potential of IFNs in skin cancer treatment, the toxicity profile often prevents the completion of treatment and further expansion of its clinical application. Type I and III IFNs use the same Janus Kinases (JAKs) for signal transduction, which are pathways initiated at a cell surface receptor that mediates the activation of target genes in the nucleus, based on this shared signaling pathway. Due to selective tumor targeting and the ability to generate both innate and adaptive immune responses, we concluded that type III IFNs have minimal side effects compared with established treatments due to selective tumor targeting. While IFN-λ, a type III IFN, shows therapeutic potential as stand-alone or in combination with another IFN, further studies need to be conducted to explore the therapeutic potential of IFN-λ in skin cancer and the underlying physiological roles and mechanisms of action. In this review, we evaluate whether treatment of skin cancer with type III IFN will have minimal side effects compared with established treatments.
干扰素（IFNs）已在多种皮肤癌，特别是鳞状细胞癌（SCC）、基底细胞癌（BCC）和黑色素瘤中显示出治疗潜力。I型干扰素在皮肤癌中发挥抗肿瘤作用的确切机制仍在研究中。然而，对于特定患者群体，病灶内注射I型干扰素可作为手术的替代方法，并且高剂量全身干扰素治疗已显示对可手术的高危或转移性黑色素瘤患者有前景。尽管干扰素在皮肤癌治疗中具有治疗潜力，但其毒性特征常常妨碍治疗的完成及其临床应用的进一步扩展。I型和III型干扰素利用相同的 Janus 激酶（JAKs）进行信号转导，基于这一共享信号通路，该信号转导是在细胞表面受体启动的途径，介导细胞核中靶基因的激活。由于具有选择性肿瘤靶向性以及产生先天性和适应性免疫反应的能力，我们得出结论，与既定治疗方法相比，III型干扰素由于选择性肿瘤靶向性而副作用最小。虽然III型干扰素IFN-λ作为单一治疗或与另一种干扰素联合使用显示出治疗潜力，但需要进一步研究以探索IFN-λ在皮肤癌中的治疗潜力以及潜在的生理作用和作用机制。在本综述中，我们评估与既定治疗方法相比，用III型干扰素治疗皮肤癌是否副作用最小。
