Targeting tubulin isotypes in cancer

微管蛋白是细胞蛋白质的一个家族，包括a-微管蛋白和b-微管蛋白，它们继续形成微管;微管在细胞中执行各种功能，例如协调细胞内的运输和调节细胞分裂。同种型存在于α-微管蛋白和β-微管蛋白两者中，其可以在其细胞定位或表达水平上不同。BIII-微管蛋白是微管蛋白同种型的一个实例。由于微管能够调节细胞分裂等过程，因此微管已成为各种化疗和抗癌药物的重要靶点。已知许多结合到在α-和β-微管蛋白上发现的口袋以诱导微管稳定或解聚，从而停止细胞分裂。例如，紫杉醇（Paclitaxel），也称为紫杉醇（Taxol），是一种来自太平洋紫杉树的化疗药物，它与位于B-微管蛋白上的紫杉烷结合口袋结合，诱导微管稳定。然而，现在也已经确定某些微管蛋白同种型可以在癌细胞中上调-已经发现BIIII-微管蛋白在乳腺癌细胞中上调。此外，这些细胞也显示出对紫杉醇等药物的耐药性，从而引发了特定微管蛋白同种型是否在癌症耐药性中发挥作用的问题。此外，缺乏对不同微管蛋白同种型与癌症药物的结合亲和力的表征。本项目旨在确定微管蛋白同种型与抗癌药物的结合亲和力，并研究如何提高不同微管蛋白与抗癌药物的亲和力。从长远来看，这可能会导致根据癌细胞中微管蛋白同种型的表达，为患者提供更特异和有效的癌症药物处方。

Tubulins are a family of cellular proteins, including a- and B-tubulin, which go on to form microtubules; microtubules perform a variety of functions in the cell, such as coordinating transport within the cell and regulating cell division. Isotypes exist in both a- and B-tubulins, which can differ in their cellular localisation or level of expression. BIII-tubulin is an example of a tubulin isotype. Since microtubules are able to regulate processes such as cell division, microtubules have become an important target for various chemotherapies and anti-cancer drugs. Many are known to bind to pockets found on both the a- and B-tubulins to induce microtubule stabilisation or depolymerisation in order to halt cell division. For instance, Paclitaxel, otherwise known as Taxol, is a chemotherapeutic drug derived from the pacific yew tree, that binds to a taxane binding pocket located on B-tubulins, inducing microtubule stabilisation. However, it has also now been established that certain tubulin isotypes can become upregulated in cancer cells - BIII-tubulins has been found to be upregulated in breast cancer cells. Moreover, these cells have also shown to be more resistance to drugs such as Paclitaxel, thereby leading to the question of whether specific tubulin isotypes play a role in cancer drug resistance. Furthermore, there is a lack of characterisation on the binding affinities of different tubulin isotypes to cancer drugs. This project aims to determine the binding affinities of tubulin isotypes to cancer drugs, and study how cancer drugs affinity could be improved for different tubulin. In the long term, this may potentially lead to more specific and effective prescription of cancer drugs to patients depending on the expression of tubulin isotypes in cancer cells.