Roles of Impaired Apoptosis and Differentiation in Tumourigenesis and Therapy

该项目的十个科学实验室联合起来研究肿瘤发展的两种方式。这两项研究都特别有趣，因为它们提出了战胜癌症的新方法。我们的大多数组织在一生中通过产生新细胞而不断更新。因此，每个组织中的许多老细胞必须死亡以维持适当的细胞数量。为了消除不再需要的或已经受损的细胞，身体已经发展出一种称为细胞凋亡的显著细胞自杀过程。然而，不幸的是，我们细胞中的基因偶尔会发生随机事故，从而阻止细胞凋亡机制的启动。在这种情况下，细胞不会在它应该死亡的时候死亡，并且通过不断分裂，最终可能导致癌症。然而，由于大多数癌细胞仍然保留了大多数细胞凋亡机制，一种能够开启这种自然细胞死亡机制的药物将为癌症治疗提供一种有希望的新方法。鉴别和开发这类药物是该项目的一个主要长期目标。我们项目的另一个重点是干细胞。这些罕见的细胞具有生成整个组织的非凡能力。例如，我们的一个实验室已经鉴定出可以产生乳腺中所有细胞的干细胞。干细胞几乎无限的再生能力有一个内在的危险。如果干细胞获得了过度增殖的能力，它可以继续形成肿瘤。事实上，许多癌症研究人员现在怀疑是肿瘤内罕见的干细胞导致了肿瘤不可阻挡的生长。如果肿瘤的生长是由干细胞维持的，那么开发针对这些罕见的癌症干细胞而不仅仅是大部分肿瘤细胞的新疗法将是至关重要的。这是我们项目的另一个关键的长期目标。

The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remarkable cell suicide process termed apoptosis. Unfortunately, however, occasionally a random accident to the genes in one of our cells prevents the machinery for apoptosis from being turned on. In that case, the cell will not die when it should and, by continually dividing, it may eventually give rise to a cancer. Since most cancer cells still retain most of the machinery for apoptosis, however, a drug that could switch on this natural cell death machinery would provide a promising new approach to cancer therapy. Identifying and developing such drugs is one major long-term goal of this program. The other focus of our program concerns stem cells. These are rare cells with the remarkable ability to generate an entire tissue. For example, one of our laboratories has identified stem cells that can generate all the cells in the breast. The almost unlimited regenerative capacity of stem cells has a built-in danger. If a stem cell acquires the ability to proliferate excessively, it can go on to form a tumour. Indeed, many cancer researchers now suspect that rare stem cells within a tumour cause its inexorable growth. If tumour growth is maintained by stem cells, it will be essential to develop new forms of therapy that target these rare cancer stem cells rather than merely the bulk of the tumour cells. This is another key long-term goal of our program.