基于化疗压力下乳腺癌细胞亚群生长规律的乳腺癌化疗耐药时机预测模型研究

Chemotherapy is an important means of adjuvant systemic therapy for breast cancer, and chemoresistance is commonly seen in the treatment. Due to lack of observation indicators in the adjuvant chemotherapy, it is difficult to predict the timing of chemotherapy resistance. Molecular typing is an independent predictor of chemotherapy sensitivity in breast cancer. Current research and our study found that the ratio of isolated and purified breast cancer cells with different molecular subtypes after culture would return to the same equilibrium state as before sorting, while the ratio of tumor cells of different molecular subtypes after chemotherapy would reach a new equilibrium state, which indicated that the ratio change of different molecular subtype tumor cells could be considered as an indicator for chemoresistance. In this project, the growth pattern of different molecular subtype cells after different drug administration and the continuous change of cell ratio will be observed firstly, then based on those data, a mathematical model will be established to explain the causes and rules, as well as to predict the timing of chemotherapy resistance. Finally, the model will be validated and revised based on the data of animal experiments and clinical specimens. The results of this research will promote our knowledge on the growth pattern of various molecular subtype breast cancer cells during chemotherapy, and provide a rational and effective tool for predicting chemotherapy resistance timing.

化疗是乳腺癌的重要治疗手段，而耐药是化疗的常见问题。辅助化疗中由于缺乏观测指标，耐药发生难以实时监测，因此预测耐药发生时机十分重要。分子分型是乳腺癌化疗敏感性的独立预测因素。国外研究和我们的同期研究均发现分选纯化的各分子亚型乳腺癌细胞经过培养后，各群细胞比例将回归到与分选前相同的平衡状态，而化疗后各分子亚型细胞比例将到达新的平衡态。同时由于化疗将富集耐药肿瘤细胞，推测化疗中各分子亚型细胞比例变化可能是乳腺癌化疗耐药的重要预警指标。鉴于数学模型能较好地模拟和预测细胞的生长规律，本项目拟首先针对体外实验中化疗条件下乳腺癌各分子亚型细胞的生长特点，检测其比例的连续变化，构建合适的数学模型阐释其原因和规律，并预测耐药发生的时机；再通过动物实验和临床数据对模型进行验证和修正。结果有助于深入对化疗过程中各分子亚型乳腺癌细胞生长规律的认识，并为预测乳腺癌化疗耐药时机以及时调整化疗方案提供合理有效的工具。