Department of Surgery, NorthShore University HealthSystem, Affiliate of University of Chicago Pritzker School of Medicine, Evanston, Illinois.
Department of Nephro-Urologic Surgery and Andrology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Prostate. 2019 Feb;79(3):259-264. doi: 10.1002/pros.23730. Epub 2018 Oct 28.
The tyrosine kinase inhibitors (TKI), imatinib and nilotinib, are used to treat chronic myelogenous leukemia (CML). In three CML patients being monitored for urologic diseases, we observed that switching of TKI therapy affected prostate-specific antigen (PSA) titers. Urologists and other medical professionals need to be aware of the potential side-effects of drugs that patients may be receiving for other indications to modify this important prostate diseases indicator. TKIs may affect PSA titers independent of prostate growth or volume.
We followed PSA levels in urology patients who were also undergoing TKI treatment for CML. We determined the effects of nilotinib and imatinib on proliferation, AR and PSA expression in the LNCaP and 22Rv1 prostate cancer (PCa) cell lines using real-time PCR and Western blotting.
Clinically, nilotinib and dasatinib reversibly reduced PSA titers compared to imatinib. At high doses nilotinib and imatinib both demonstrated antiproliferative effects in the PCa cells. At low doses expression of AR and PSA was decreased by both drugs, at mRNA and protein levels. Nilotinib exerted greater effects at lower doses than imatinib.
Nilotinib down-regulates serum PSA in patients being treated for non-urological indications, potentially masking a clinical useful marker, we cannot exclude a similar but smaller effect of imatinib. Nilotinib and imatinib both decreased AR and PSA expression in PCa cell lines with the nilotinib effect evident at lower doses. Urologists must appreciate the effects of drugs provided for other diseases on PSA titers and be aware that sudden changes may not reflect underlying prostatic disease.
酪氨酸激酶抑制剂（TKI）伊马替尼和尼罗替尼用于治疗慢性髓性白血病（CML）。在三名接受泌尿科疾病监测的 CML 患者中，我们观察到 TKI 治疗的转换影响了前列腺特异性抗原（PSA）滴度。泌尿科医生和其他医疗专业人员需要意识到患者可能因其他适应症而接受的药物的潜在副作用，以修改这个重要的前列腺疾病指标。TKI 可能会影响 PSA 滴度，而与前列腺生长或体积无关。
我们跟踪了同时接受 TKI 治疗 CML 的泌尿科患者的 PSA 水平。我们使用实时 PCR 和 Western blot 确定尼罗替尼和伊马替尼对 LNCaP 和 22Rv1 前列腺癌（PCa）细胞系中增殖、AR 和 PSA 表达的影响。
临床上，尼罗替尼和达沙替尼与伊马替尼相比可可逆地降低 PSA 滴度。高剂量时，尼罗替尼和伊马替尼均在 PCa 细胞中显示出抗增殖作用。低剂量时，两种药物均降低了 AR 和 PSA 的表达，mRNA 和蛋白水平均降低。尼罗替尼在较低剂量下的作用大于伊马替尼。
尼罗替尼下调了接受非泌尿科适应症治疗的患者的血清 PSA，可能掩盖了一个临床有用的标志物，我们不能排除伊马替尼的类似但较小的作用。尼罗替尼和伊马替尼均降低了 PCa 细胞系中的 AR 和 PSA 表达，尼罗替尼的作用在较低剂量时更为明显。泌尿科医生必须注意用于治疗其他疾病的药物对 PSA 滴度的影响，并意识到突然的变化可能并不反映潜在的前列腺疾病。
