以作用機轉為基礎之標靶藥物在眼科治療之角色

標靶治療是近年來疾病的新興治療策略，廣義而言是瞄準特定的致病機轉，治療疾病本身並同時降低副作用。本文首先介紹ROCK抑制劑、鈣調磷酸酶抑制劑（calcineurin inhibitors）、整合素抑制劑（integrin inhibitors）、抗血管內皮生長因子藥物（anti-VEGF therapies）等藥物於眼科的應用。接著討論眼科癌症，包括眼內淋巴癌與葡萄膜黑色素瘤的標靶治療。上述藥物參與的生理作用涵蓋血管新生、免疫反應與致癌機制。本文主要介紹這些標靶藥物的藥理機轉與新藥在疾病治療上的角色，並輔以當前的尚待克服的挑戰與研究目標，期待結合這些基礎藥理機轉與臨床治療上的證據，可指引未來眼科精準治療的方向。

關鍵字

標靶治療； Rho相關蛋白酶；鈣調磷酸酶抑制劑；整合素；抗血管內皮生長因子；眼內淋巴癌；葡萄膜黑色素瘤

並列摘要

Targeted therapies have become emerging treatment strategies for various ocular diseases. These treatments exploit novel targets and mechanisms with an aim to better control the diseases with reduced adverse effects. In this article, we introduced the application of targeted therapy in ophthalmology, including ROCK (Rho-kinase) inhibitors, calcineurin inhibitors, integrin inhibitors and anti-VEGF(vascular endothelial growth factor) therapies. We also discussed targeted therapies for ocular cancers including primary intraocular lymphoma and uveal melanoma. These topics cover a wide spectrum of biological processes, such as vascular proliferation, immune response and oncogenesis. For each topic, we briefly presented the underlying mechanisms, along with the corresponding drugs and their role in current ocular disease regimens. We further included some ongoing challenges and research directions to solve them. Combining these pharmacological knowledge and clinical evidence may shed light on ideas towards future precise treatments in ophthalmology.

並列關鍵字

targeted therapy ； ROCK ； calcineurin ； integrin ； VEGF ； intraocular lymphoma ； uveal melanoma

參考文獻

Renouf DJ, Velazquez-Martin JP, Simpson R, et al. Ocular toxicity of targeted therapies. J Clin Oncol 2012;30:3277-86.

Wang SK, Chang RT. An emerging treatment option for glaucoma: Rho kinase inhibitors. Clin Ophthalmol 2014;8:883-90.

Okumura N, Sakamoto Y, Fujii K, et al. Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction. Sci Rep 2016;6:26113.

Kinoshita S, Koizumi N, Ueno M, et al. Injection of cultured cells with a ROCK inhibitor for bullous keratopathy. N Engl J Med 2018;378:995-1003.

Ren R, Li G, Le TD, et al. Netarsudil increases outflow facility in human eyes through multiple mechanisms. Invest Ophthalmol Vis Sci 2016;57:6197-209.

國際替代計量

以作用機轉為基礎之標靶藥物在眼科治療之角色

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