Tchelebi Leila, Ashamalla Hani, Graves Paul R
Department of Radiation Oncology, New York Methodist Hospital, 506 6th Street, Brooklyn, NY, 11215, USA.
Subcell Biochem. 2014;85:133-59. doi: 10.1007/978-94-017-9211-0_8.
In addition to playing roles in the genesis and progression of cancer, mutant p53 also appears to play a significant role in the response to cancer therapy. In response to chemotherapy and radiation, two mainstays of cancer treatment, most cancer cells harboring p53 mutations show a reduced sensitivity compared to cells lacking p53 or those with wild type p53. However, there are also many instances where mutant p53 has shown no effect or enhances cellular sensitivity to chemotherapy and radiation. Similar to the in vitro cellular studies, the majority of clinical studies show a correlation between the presence of mutant p53 in patient tumors and adverse outcomes following treatment with chemotherapy agents or radiation in comparison to tumors with wild-type p53. However, it still remains unclear whether the presence of mutant p53 in tumors can serve as a reliable prognostic factor and aid in treatment planning. Thus, as genomic analysis of patient tumors becomes more cost effective, the role of mutant p53 in tumor responses from cancer therapy ultimately needs to be addressed. This chapter will discuss current mechanisms of how p53 mutations affect cellular responses to chemotherapy and radiation and discuss patient outcomes based on p53 status.
除了在癌症的发生和发展中发挥作用外，突变型p53似乎在癌症治疗反应中也起着重要作用。在癌症治疗的两大主要手段——化疗和放疗中，与缺乏p53或具有野生型p53的细胞相比，大多数携带p53突变的癌细胞表现出较低的敏感性。然而，也有许多情况表明突变型p53对化疗和放疗没有影响或增强了细胞的敏感性。与体外细胞研究类似，大多数临床研究表明，与具有野生型p53的肿瘤相比，患者肿瘤中存在突变型p53与化疗药物或放疗治疗后的不良预后相关。然而，肿瘤中突变型p53的存在是否可作为可靠的预后因素并有助于治疗规划仍不清楚。因此，随着对患者肿瘤的基因组分析变得更具成本效益，突变型p53在癌症治疗引起的肿瘤反应中的作用最终需要得到解决。本章将讨论p53突变影响细胞对化疗和放疗反应的当前机制，并根据p53状态讨论患者的预后情况。
