断糖，饿死癌细胞可能是将来癌症治疗的关键
Starving cancer cells of sugar could be the key to future treatment
翻译：蓝山
我们身体里所有细胞的死亡都是程序性的。随着年龄的增长，我们的细胞积累有毒的分子，使它们生病。作为回应，它们最终会分解，为新的健康细胞的生长扫清障碍。这种“程序性细胞死亡”是我们生活中一个自然而重要的部分。每天，数以亿计的细胞都像这样死去，以便整个有机体继续正常运转。
但与任何程序一样，错误可能发生，受伤的细胞会继续生长和分裂。这些受损的细胞最终会恶变并产生肿瘤。为了避免这种程序性细胞死亡，癌细胞重组了它们的新陈代谢，这样它们就可以欺骗死亡并无限增殖。
癌症研究人员几十年来都知道，肿瘤的新陈代谢比我们身体的正常细胞更快。一个典型的例子就是癌细胞增加葡萄糖的消耗，以刺激它们的快速生长和对程序性细胞死亡的攻击。这意味着，限制癌细胞的葡萄糖消耗正在成为癌症治疗的一个有吸引力的工具。
一个新的希望?
你可能已经见过一些文章或网站主张，让病人断糖对清除肿瘤至关重要，或者少吃糖可以降低患癌症的风险。事情没那么简单。癌细胞总是能找到替代燃料的方法，不管我们摄取的糖分有多小。吃糖和患癌症之间没有直接的联系，如果你对你的饮食有怀疑，最好和你的医生谈谈。
研究人员已经证明，癌细胞利用葡萄糖来生成肿瘤快速生长所需的细胞化合物的构件。癌细胞还用它来生成分子，以防止活性氧的有毒物质积累，这些分子会破坏细胞，从而激活程序性细胞死亡。这意味着葡萄糖可以作为防止细胞死亡的保护剂。
如果我们吃的糖量不影响这个过程，我们需要回答的问题是癌细胞如何被指示消耗更多的葡萄糖。谁在给油箱加油?我们已经发现，让肿瘤以这种方式逃避其自然死亡原因的是一种蛋白质，它在几乎所有人类癌症中都过度产生，但在正常细胞中却没有。
涡轮增压的增长
在最近发表在《自然通讯》(Nature Communications)杂志上的一项研究中，我们发现，癌细胞会刺激被称为PARP14的蛋白质的过度生产，从而使它们能够利用葡萄糖来增强其生长，并逃逸细胞死亡的自然检查。通过基因和分子生物学的结合，我们也证明了抑制或降低癌细胞中PARP14的水平会使癌细胞死亡。
最好的消息是，通过比较癌症患者和已经死亡的患者的癌症组织(活检)，我们发现那些已经死亡的患者的PARP14水平明显更高。这意味着癌症组织中PARP14的水平也可以预测癌症的侵袭程度，以及病人存活的可能性。
这意味着，一种可以阻断这种蛋白质的治疗，可能代表着癌症治疗未来的一场重大变革。更重要的是，与传统的化疗和放射治疗不同，使用PARP14抑制剂只会杀死癌细胞，而不是健康的细胞。下一步是设计并生成新的药物，以阻断这种蛋白质，并研究如何在病人中安全地使用它们。
参考文献：
Starving cancer cells of sugar could be the key to future treatment
September 24, 2015 2.36am AEST
All the cells in our bodies are programmed to die. As they get older, our cells accumulate toxic molecules that make them sick. In response, they eventually break down, clearing the way for new, healthy cells to grow. This “programmed cell death” is a natural and essential part of our wellbeing. Every day, billions of cells die like this in order for the whole organism to continue functioning as it is supposed to.
But as with any programme, errors can occur and injured cells that are supposed to die continue to grow and divide. These damaged cells can eventually become malignant and generate tumours. In order to avoid their programmed cell death in this way, cancer cells reorganise their metabolism so they can cheat death and proliferate indefinitely.
Cancer researchers have known for decades that tumours use a faster metabolism than normal cells in our body. One classic example of this is that cancer cells increase their consumption of glucose to fuel their rapid growth and strike against programmed cell death. This means that limiting glucose consumption in cancer cells is becoming an attractive tool for cancer treatments.
A new hope?
You may have seen articles or websites advocating that starving patients of sugar is crucial for getting rid of tumours or that eating less sugar reduces the risk of cancer. The story is not that simple. Cancer cells always find alternatives to fuel their tank of glucose, no matter how little sugar we ingest. There is not a direct connection between eating sugar and getting cancer and it is always advisable to talk to your doctor if you have doubt about your diet.
Researchers have demonstrated that cancer cells use glucose to generate the building blocks of the cellular compounds needed for rapid tumour growth. They also use it to generate molecules that guard against the toxic accumulation of reactive oxygen species, the cell-damaging molecules that activate programmed cell death. This means that glucose serves as a master protector against cell death.
If the amount of sugar we eat doesn’t affect this process, the question we need to answer is how the cancer cells are instructed to consume more glucose. Who is filling the fuel tank? We have discovered that what allows tumours to evade their natural cause of death in this way is a protein that is overproduced in virtually every human cancer but not in normal cells.
Turbocharged growth
In a recent study published in Nature Communications we showed that cancer cells stimulate the over-production of the protein known as PARP14, enabling them to use glucose to turbocharge their growth and override the natural check of cell death. Using a combination of genetic and molecular biology approaches, we have also demonstrated that inhibiting or reducing levels of PARP14 in cancer cells starves them to death.
The best news is that by comparing cancer tissues (biopsies) from patients that has survived cancer and those that have died, we have found that levels of PARP14 were significantly higher in those patients that have died. This means that levels of PARP14 in cancer tissues could also predict how aggressive the cancer would be and what the chances are of a patient’s survival.
This means that a treatment which could block the protein could represent a significant revolution in the future of cancer treatment. What’s more, unlike traditional chemotherapy and radiotherapy, the use of PARP14 inhibitors would only kill cancer cells and not healthy ones. The next step is to design and generate new drugs that can block this protein and work out how to use them safely in patients.