Roles of Impaired Apoptosis and Differentiation in Tumourigenesis and Therapy

该计划中的十个科学实验室联手研究肿瘤发展的两种方式。这两种方法都特别令人感兴趣，因为它们提出了克服癌症的新方法。我们的大部分组织在一生中通过产生新的细胞而不断更新。因此，每个组织中的许多旧细胞必须死亡才能保持适当的细胞数量。为了清除不再需要或已经受损的细胞，人体发展了一个非凡的细胞自杀过程，称为细胞凋亡。然而，不幸的是，偶尔，我们其中一个细胞中的基因的随机事故会阻止细胞凋亡机制的启动。在这种情况下，细胞不会在应该死亡的时候死亡，通过不断分裂，它可能最终会导致癌症。然而，由于大多数癌细胞仍然保留着大部分的细胞凋亡机制，一种可以启动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。识别和开发这类药物是该计划的一个主要长期目标。我们项目的另一个关注点是干细胞。这些是罕见的细胞，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在乳房中产生所有细胞的干细胞。干细胞几乎无限的再生能力存在着内在的危险。如果干细胞获得了过度增殖的能力，它可能会继续形成肿瘤。事实上，许多癌症研究人员现在怀疑，肿瘤中罕见的干细胞导致了它的不可阻挡的生长。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的新的治疗形式将是至关重要的，而不仅仅是大部分肿瘤细胞。这是我们计划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.