A Mathematical Model of Intermittent Androgen Suppression for Prostate Cancer
A Mathematical Model of Intermittent Androgen Suppression for Prostate Cancer
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DOI：
10.1007/s00332-008-9031-0
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发表时间：
2008-12-01
影响因子：
3
通讯作者：
Aihara, Kazuyuki
中科院分区：
文献类型：
--
作者：
Ideta, Aiko Miyamura;Tanaka, Gouhei;Aihara, Kazuyuki
几十年来，雄激素抑制一直是治疗晚期前列腺癌的主要方式。尽管雄激素剥夺最初是有效的，但由于所谓的雄激素非依赖性肿瘤细胞的增殖，大多数患者在几年内经历复发。布鲁乔夫斯基等人。在动物模型中表明，与连续雄激素抑制（CAS）相比，间歇性雄激素抑制（IAS）可以延长复发时间。因此，IAS 有望提高临床疗效，同时减少不良反应并改善患者停药期间的生活质量。本文提出了一个数学模型，根据血清前列腺特异性抗原 (PSA) 的监测来描述 IAS 治疗下前列腺肿瘤的生长。通过将癌症肿瘤视为雄激素依赖性和雄激素非依赖性细胞的混合组合，我们研究了 CAS 和 IAS 在影响雄激素非依赖性复发的因素方面的差异。数值和分叉分析显示了肿瘤生长和复发时间如何受到雄激素非依赖性细胞的净生长速率、IAS治疗方案以及从雄激素依赖性细胞到雄激素非依赖性细胞的突变率的影响。
For several decades, androgen suppression has been the principal modality for treatment of advanced prostate cancer. Although the androgen deprivation is initially effective, most patients experience a relapse within several years due to the proliferation of so-called androgen-independent tumor cells. Bruchovsky et al. suggested in animal models that intermittent androgen suppression (IAS) can prolong the time to relapse when compared with continuous androgen suppression (CAS). Therefore, IAS has been expected to enhance clinical efficacy in conjunction with reduction in adverse effects and improvement in quality of life of patients during off-treatment periods. This paper presents a mathematical model that describes the growth of a prostate tumor under IAS therapy based on monitoring of the serum prostate-specific antigen (PSA). By treating the cancer tumor as a mixed assembly of androgen-dependent and androgen-independent cells, we investigate the difference between CAS and IAS with respect to factors affecting an androgen-independent relapse. Numerical and bifurcation analyses show how the tumor growth and the relapse time are influenced by the net growth rate of the androgen-independent cells, a protocol of the IAS therapy, and the mutation rate from androgen-dependent cells to androgen-independent ones.