研究人员发现潜在的目标为“肝癌undruggable”形式
在一个新的方法来寻找治疗肝癌，MSK科学家发现这种高侵袭性前列腺癌的一个潜在的药物靶标。
越来越多的科学家正在寻找新的癌症治疗方法。在最近的努力集中在肝细胞癌（HCC），一种常见的侵袭性肝癌的形成，一个团队的纪念斯隆-凯特琳研究人员发现了一种方法来阻止癌细胞的小鼠，为制定有针对性的药物对它打开了新的可能性。
而不是只专注于基因的已知驱动癌症&mdash；而没有有效的药物可能存在&mdash；研究人员针对肿瘤细胞的药物已经上市或正在开发的其他基因。这项研究是由生物学家史葛Lowe的癌症生物学和遗传学计划的主席和杰弗里Beene癌症研究中心，并在杂志报道基因与发展月。
没有明显的药物靶点
根据一些估计，肝癌是全球癌症相关死亡的第三大原因，其发病率呈上升趋势。在肝癌肿瘤来源于患者的基因组研究，科学家在MSK和其他地方已经发现了一些基因的改变是负责驾驶的疾病，包括基因突变MYC。
But to their disappointment, none of these mutations are “druggable” — in other words, patients whose tumors carry these alterations can’t be offered a drug or a clinical trial that would potentially benefit them。
In many other cancers, such as lung cancer and melanoma, molecular characterization has led to the discovery of mutations that make tumor cells vulnerable to specific targeted therapies。 “But HCC remains a disease for which no effective drugs exist,” Dr。 Lowe says。 “Even though we’ve learned about a number of things that are important in keeping these cancers alive, genomic studies haven’t led to any obvious ways to treat them。”
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Rather than looking for changes in the DNA sequence of HCC tumors, Dr。 Lowe and his co-workers set out to try a different approach。 His lab developed methods to shut down the activity of almost every gene in a cell one by one, to determine what the gene’s biological function is or whether the cell needs it to grow or survive。 These methods, which are based on a technology called RNA interference (RNAi), also make it possible to screen cancer cells for potential drug targets。
“The problem with RNAi screens is they are very challenging and time consuming,” Dr。 Lowe says, “and since HCC is a lethal cancer, we just can’t spend a decade looking for a drug。”
To speed the process, the researchers chose to confine the search to genes for which drugs already existed or were being developed。 Following this approach, they identified a number of genes whose activity could be therapeutically stifled to kill HCC cells。
回到顶部治疗某些肿瘤的门口
研究人员发现，靶向的基因之一，它编码一种酶叫做CDK9，可能在肿瘤的患者的一个子集，特别有效的携带突变MYC gene。 “Our results demonstrate how CDK9 and MYC ‘talk’ to each other to drive tumor progression,” Dr。 Lowe explains, “and that inhibiting CDK9 with a type of drug called a kinase inhibitor could be an effective way to control that progression。”
The CDK9-inhibitors that currently exist are not good enough to be tested in patients, however。 “The compounds are not very specific and there’s a risk they could interfere with other proteins whose molecular structure is similar to that of CDK9,” he says。 “This could lead to adverse side effects。”
Yet, he adds, these drug molecules do provide a starting point for chemists to develop new, more-precise compounds that potentially could be used to target HCC cells without damaging normal cells。
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