Chemical bioreductive approaches to targeted radiosensitisation and imaging of tumours

人体内的所有细胞都需要氧气才能生存。氧气不足的情况，例如心脏病发作和中风，被称为缺氧。人体的设计是为了抵抗肿瘤的形成，所以任何发展中的肿瘤都面临着许多挑战，其中之一是氧气供应。不幸的是，肿瘤设法克服了这一挑战，并在或多或少的程度上欺骗身体提供氧气。肿瘤细胞，接受不足的氧气和缺氧，适应这种条件，并在这样做变得更强大，更难以杀死。特别是，缺氧肿瘤细胞比接受足够氧气的肿瘤细胞更耐放射治疗。显然，由于所有接受癌症治疗的人中有50%接受放射治疗，因此找到使这种治疗对低氧肿瘤细胞更有效的方法是重要的。目前，癌症的缺氧程度越高，放射治疗的效果就越差。这项新工作是牛津大学化学系和肿瘤学的合作，他们共同提出了一种解决缺氧肿瘤细胞的方法。到目前为止，化学家们已经制造出一种药物，它可以杀死缺氧的肿瘤细胞，使它们对放射治疗更敏感，但不会伤害正常细胞。生物学家已经在实验室中生长的缺氧人类癌细胞上测试了这种药物，下一步，我们希望能够制造更多的这种新药，并在实验室和小鼠中进一步测试。这种测试是必不可少的，如果这种药物要发展到与癌症患者的放射治疗相结合。我们还计划修改药物，使其在缺氧条件下变得活跃时立即发出荧光。这将使生物学测试变得更加容易，因为我们将能够准确地看到它何时何地变得活跃。总之，肿瘤缺氧程度越高，患者死亡的可能性就越大。因此，我们专门针对这些细胞的方法可能会对患者的生存产生重大影响。

All cells in the human body require oxygen to survive. The condition where insufficient oxygen is available, as occurs in heart attacks and strokes for example, is referred to as hypoxia.The human body is designed to resist the formation of tumours, so any developing tumour faces many challenges, one of which is oxygen supply. Unfortunately, tumours manage to overcome this challenge and cheat the body into providing oxygen to a greater or lesser extent.The tumour cells, which receive insufficient oxygen and experience hypoxia, adapt to this condition and in so doing become stronger and more difficult to kill.In particular, hypoxic tumour cells are more resistant to radiotherapy than tumour cells that receive sufficient oxygen.Clearly, as 50% off all people treated for cancer receive radiotherapy, it is important to find ways of making this treatment more effective against hypoxic tumour cells. Presently, the more hypoxic the cancer the less effective is the radiotherapy treatment.This new work is a collaboration between the Chemistry Department and Oncology at Oxford who together have come up with a way to tackle hypoxic tumour cells.So far, the chemists have made a drug, which can kill hypoxic tumour cells and make them more susceptible to radiotherapy, but does not harm normal cells. The biologists have tested this drug on hypoxic human cancer cells grown in the laboratoryAs a next step, we would like to be able to make more of this new drug and to test it further both in the laboratory and in mice. This kind of testing is essential if this drug is ever going to progress to being useful in combination with radiotherapy for cancer patients. We also plan to modify the drug so that it becomes fluorescent as soon as it becomes active in hypoxic conditions. This will make the biological testing much easier as we will be able to see exactly when and where it becomes active.In summary, the more hypoxic a tumour is the more likely it is to kill the patient. Therefore, our approach to target these cells specifically could have a major impact on patient survival.