ALDH家族被报道参与肿瘤复发、转移及耐药。以往研究表明细胞浆型ALDH是决定ALDH活性与功能的主要因素，而对线粒体型ALDH2的肿瘤生物学角色尚不清楚。我们前期结果表明，微管蛋白抑制剂（TI）耐药细胞干性特征增强，ALDH活性增加，且ALDH2表达明显增高；沉默ALDH2或靶向抑制后，ALDH活性显著下降、耐药能力减弱、干性特征消失，提示ALDH2在TI耐药过程的关键作用。此外，对其表达调控机制研究发现，DNA甲基化和组蛋白修饰扮演着重要角色。然而，关于它的确切失调机制，在耐药过程中的角色，以及靶向干预的治疗价值还需进一步阐明。为此，本课题拟采用多种技术手段：1）阐明ALDH2在耐药细胞的失调机制，并揭示ALDH2在干性维持及其所介导的TI耐药中的角色特点，以期阐释肿瘤耐药的发生发展过程；2）探索靶向干预ALDH2对TI耐药逆转作用的影响，为靶向逆转肿瘤耐药策略提供新途径。

ALDH family is involved into tumor recurrence, metastasis and drug resistance. Among ALDH family members, cytoplasm ALDHs were considered as the main factor to determine ALDH activity and promote malignancy. However, the role of the ALDH2, a mitochondrial subtype, in tumor biology is still not well known. In our precious study, we found that there was an increasing of ALDH activity and an enhancement of cancer stem cell characteristics in microtubule inhibitor resistant cancer cells as compared to counterpart cells. Interestingly, among the ALDH members, only ALDH2 showed an increasing expression in the drug resistant cells. Importantly, silencing ALDH2 by specific siRNA or blocking ALDH2 by disulfiram, an ALDH inhibitor, could decrease the ALDH activity, reverse drug resistance, and attenuate cancer stem cell characteristics in drug resistant cells, suggesting ALDH2 plays a crucial role in the microtubule inhibitor resistance. Furthermore, our data demonstrated that the epigenetic regulation, including DNA methylation and histone modification, might be contributed to the upregulation of ALDH2 in drug resistant cells. Based on the above results, we plan to: 1) elucidate the regulatory mechanisms of the upregulation of ALDH2 in microtubule inhibitor resistant cancer cells, and disclose the precise role of ALDH2 in the maintenance of cancer cell stemness and its mediated microtubule inhibitor resistance, which will be benefit to comprehensively understand the development and progression of tumor drug resistance；2）explore the therapeutic value of targeting ALDH2 by disulfiram in microtubule inhibitor resistance, which will provide a novel path to reverse tumor drug resistance.