Departamento de Estadística e Investigación Operativa, Universidad de Granada, Granada, Spain.
J Theor Biol. 2012 Dec 7;314:34-56. doi: 10.1016/j.jtbi.2012.08.006. Epub 2012 Aug 11.
Modeling the effect of therapies in cancer animal models remains a challenge. This point may be addressed by considering a diffusion process that models the tumor growth and a modified process that includes, in its infinitesimal mean, a time function modeling the effect of the therapy. In the case of a Gompertz diffusion process, where a control group and one or more treated groups are examined, a methodology to estimate this function has been proposed by Albano et al. (2011). This method has been applied to infer the effect of cisplatin and doxorubicin+cyclophosphamide on breast cancer xenografts. Although this methodology can be extended to other diffusion processes, it has an important restriction: it is necessary that a known diffusion process adequately fits the control group. Here, we propose the use of a stochastic process for a hypothetical control group, in such a way that both the control and the treated groups can be modeled by modified processes of the former. Thus, the comparison between models would allow estimating the real effect of the therapy. The new methodology has been validated by inferring the effects in breast cancer models, and we have checked the robustness of the procedure against the choice of stochastic model for the hypothetical control group. Finally, we have also applied the methodology to infer the effect of a therapeutic peptide and ovariectomy on the growth of a breast cancer xenograft, and its efficiency in modeling the effect of different treatments in the absence of control group data is shown.
在癌症动物模型中模拟治疗效果仍然是一个挑战。通过考虑一个可以模拟肿瘤生长的扩散过程和一个包含治疗效果时间函数的修正过程,可以解决这一问题。在 Gompertz 扩散过程中,当检查对照组和一个或多个治疗组时,Albano 等人(2011)提出了一种估计该函数的方法。该方法已应用于推断顺铂和多柔比星+环磷酰胺对乳腺癌异种移植的作用。虽然这种方法可以扩展到其他扩散过程,但它有一个重要的限制:需要一个已知的扩散过程来充分拟合对照组。在这里,我们提出使用随机过程来假设对照组,以便通过对前者的修正过程来模拟对照组和治疗组。因此,模型之间的比较可以估计治疗的实际效果。新方法已通过推断乳腺癌模型中的效果得到验证,并且我们已经检查了针对假设对照组的随机模型选择的稳健性。最后,我们还将该方法应用于推断治疗性肽和卵巢切除术对乳腺癌异种移植生长的影响,并展示了其在没有对照组数据的情况下模拟不同治疗效果的效率。