Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3200.
Mol Biol Cell. 2019 Jul 1;30(14):1641-1644. doi: 10.1091/mbc.E19-03-0177.
Cancer treatments have, in general, targeted the cancer cell itself. This approach has often been unsuccessful in the long term, especially for solid tumors. Even targeted therapies based on sequencing cancer genomes can be thwarted by genetic heterogeneity within tumors. Furthermore, genomic instability in cancer cells accelerates the generation of variants that are resistant to the treatment. Immunotherapies and anti-angiogenic treatments, which target the tumor-interacting and tumor-adjacent cells, have overcome some of these challenges, suggesting that other methods that target wild-type cells could be valuable in arresting tumor progression. Studies in have uncovered mechanisms by which cells within an epithelium can react to neighboring cells that have genetic differences, resulting in the elimination of one population at the expense of another. Some of these mechanisms are now known to be conserved in mammals. The possibility of harnessing such mechanisms to empower normal epithelial cells to eliminate their precancerous neighbors before they develop into fully fledged cancers is an area of research that merits more attention.
癌症治疗通常针对癌细胞本身。从长期来看，这种方法往往并不成功，尤其是对于实体肿瘤。即使基于测序癌症基因组的靶向治疗也可能被肿瘤内的遗传异质性所阻碍。此外，癌细胞中的基因组不稳定性加速了对治疗产生抗性的变体的产生。靶向肿瘤相互作用和肿瘤相邻细胞的免疫疗法和抗血管生成疗法已经克服了其中的一些挑战，这表明针对野生型细胞的其他方法可能在阻止肿瘤进展方面具有重要价值。的研究揭示了上皮细胞内的细胞如何对具有遗传差异的邻近细胞做出反应，从而导致一个群体被消灭，而另一个群体受益。其中一些机制现在已知在哺乳动物中是保守的。利用这些机制来增强正常上皮细胞，在它们发展为完全成熟的癌症之前消除它们的癌前邻居，这是一个值得更多关注的研究领域。
