Rancoule Chloé, Vallard Alexis, Guy Jean-Baptiste, Espenel Sophie, Sauvaigo Sylvie, Rodriguez-Lafrasse Claire, Magné Nicolas
Institut de cancérologie Lucien-Neuwirth, département de radiothérapie, 108 bis, avenue Albert-Raimond, BP60008, 42271 Saint-Priest-en-Jarez cedex, France; Institut de physique nucléaire de Lyon (IPNL), laboratoire de radiobiologie cellulaire et moléculaire, CNRS UMR 5822, 69622 Villeurbanne, France.
LXRepair, Parvis-Louis-Néel, 38000 Grenoble, France.
Bull Cancer. 2017 Nov;104(11):962-970. doi: 10.1016/j.bulcan.2017.09.006. Epub 2017 Nov 11.
Maintaining the genetic integrity is a key process in cell viability and is enabled by a wide network of repair pathways. When this system is defective, it generates genomic instability and results in an accumulation of chromosomal aberrations and mutations that may be responsible for various clinical phenotypes, including susceptibility to develop cancer. Indeed, these defects can promote not only the initiation of cancer, but also allow the tumor cells to rapidly acquire mutations during their evolution. Several genes are involved in these damage repair systems and particular polymorphisms are predictive of the onset of cancer, the best described of them being BRCA. In addition to its impact on carcinogenesis, the DNA damage repair system is now considered as a therapeutic target of choice for cancer treatment, as monotherapy or in combination with other cytotoxic therapies, such as chemotherapies or radiotherapy. PARP inhibitors are nowadays the best known, but other agents are emerging in the field of clinical research. The enthusiasm in this area is coupled with promising results and a successful collaboration between clinicians and biologists would allow to optimize treatment plans in order to take full advantage of the DNA repair system modulation.
维持基因完整性是细胞存活的关键过程,由广泛的修复途径网络实现。当这个系统存在缺陷时,会产生基因组不稳定,导致染色体畸变和突变的积累,这些可能是各种临床表型的原因,包括患癌易感性。事实上,这些缺陷不仅会促进癌症的发生,还会使肿瘤细胞在进化过程中迅速获得突变。有几个基因参与这些损伤修复系统,特定的多态性可预测癌症的发生,其中最广为人知的是BRCA。除了对致癌作用的影响外,DNA损伤修复系统现在被认为是癌症治疗的首选治疗靶点,可作为单一疗法或与其他细胞毒性疗法(如化疗或放疗)联合使用。PARP抑制剂是目前最知名的,但临床研究领域也出现了其他药物。该领域的热情伴随着令人鼓舞的结果,临床医生和生物学家之间的成功合作将有助于优化治疗方案,以便充分利用DNA修复系统的调节作用。