Trastuzumab-Deruxtecan治療婦科癌症

The role of trastuzumab-deruxtecan in gynecological cancer

Transtuzumab deruxtecan（T-DXd）乃一單株抗體，transtuzumab經可斷裂的四胜肽作接合鏈，與topoisomerase I抑制劑deruxtecan合成的抗體藥物結合體（Antibody Drug Conjugates，ADC），用來消滅含人類上皮生長因子受器2（human epidermal growth factor receptor 2，HER2）的腫瘤細胞。當負載物（payload）deruxtecan進入腫瘤細胞後有毒殺作用，而且四週滲透擴散作用，因有很高的細胞膜穿透性，特別對HER2陽性或HER2突變的腫瘤細胞，消滅的效果甚佳。但要注意間質性肺炎疾病／肺炎的副作用，需定期追蹤、監控，一旦發現異常，可予以類固醇治療，痊癒後以超過4週的時間逐漸減少劑量。

Transtuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate(ADC) that consists of a humanized anti-human epidermal growth factor receptor 2 (HER 2) monoclonal antibody trastuzumab, covalently linked to a novel topoisomerase 1 inhibitor (deruxtecan) through a tetrapeptide cleavable linker. The high membrane permeability of the payload (deruxtecan) allows it to exert cytotoxic effects on neighboring tumor cells via bystander effects. Clinical trials have demonstrated that T-DXd exhibits significant antitumor effects across various HER2 expression levels or HER 2 mutations, including endometrial and ovarian cancers. While T-DXd has demonstrated efficacy, its safety profile, particularly concerning interstitial lung disease (ILD)/pneu-monitis, which is listed as a black boxed warning on approved labels for T-DXd. Systemic corticosteroids should be administered until improvement, followed by a gradual taper over at least four weeks.