Reddy G Kesava, Mughal Tariq I, Rini Brian I
CIG Media Group, LP, Dallas, TX, USA.
Clin Genitourin Cancer. 2006 Sep;5(2):110-3. doi: 10.3816/cgc.2006.n.026.
Mammalian target of rapamycin (mTOR) is the key regulator of cell growth and proliferation. Alterations in the mTOR signaling pathway can lead to neoplastic transformation and progression. The inhibition of mTOR blocks the progression of the cell cycle from G1 to S phase, leading to cell growth arrest and apoptosis. Thus, mTOR is a promising target for the treatment of human malignancies. Rapamycin and its analogues, including temsirolimus, everolimus, and AP23573, block the mTOR signaling pathway and induce a cellular state akin to starvation, with significant antitumor activity in a variety of malignancies, including renal cell carcinoma (RCC). Current data from ongoing clinical trials suggest that mTOR-targeted therapy with rapamycin derivatives is well tolerated with significant clinical activity in patients with advanced-stage RCC. Specifically, temsirolimus as monotherapy has demonstrated improved progression-free and overall survival in patients with poor-risk advanced-stage RCC. Everolimus has also demonstrated promising antitumor activity in patients with metastatic RCC. However, optimal dose, treatment schedule, selection of patients, and appropriate combination strategies with other novel agents need to be defined for mTOR-targeted therapies in the treatment of advanced-stage RCC.
雷帕霉素的哺乳动物靶点（mTOR）是细胞生长和增殖的关键调节因子。mTOR信号通路的改变可导致肿瘤转化和进展。抑制mTOR可阻断细胞周期从G1期到S期的进程，导致细胞生长停滞和凋亡。因此，mTOR是治疗人类恶性肿瘤的一个有前景的靶点。雷帕霉素及其类似物，包括替西罗莫司、依维莫司和AP23573，可阻断mTOR信号通路并诱导一种类似于饥饿的细胞状态，在包括肾细胞癌（RCC）在内的多种恶性肿瘤中具有显著的抗肿瘤活性。正在进行的临床试验的当前数据表明，雷帕霉素衍生物的mTOR靶向治疗耐受性良好，对晚期RCC患者具有显著的临床活性。具体而言，替西罗莫司单药治疗已在高危晚期RCC患者中显示出无进展生存期和总生存期的改善。依维莫司在转移性RCC患者中也显示出有前景的抗肿瘤活性。然而，在晚期RCC的治疗中，mTOR靶向治疗的最佳剂量、治疗方案、患者选择以及与其他新型药物的适当联合策略仍需确定。
