PDF(Pubmed)
Abstract：
CHEK2 is considered to be involved in homologous recombination repair (HRR). Individuals who have germline pathogenic variants (gPVs) in CHEK2 are at increased risk to develop breast cancer and likely other primary cancers. PARP inhibitors (PARPi) have been shown to be effective in the treatment of cancers that present with HRR deficiency-for example, caused by inactivation of BRCA1/2. However, clinical trials have shown little to no efficacy of PARPi in patients with CHEK2 gPVs. Here, we show that both breast and non-breast cancers from individuals who have biallelic gPVs in CHEK2 (germline CHEK2 deficiency) do not present with molecular profiles that fit with HRR deficiency. This finding provides a likely explanation why PARPi therapy is not successful in the treatment of CHEK2-deficient cancers.
摘要：
CHEK2被认为参与同源重组修复(HRR)。在CHEK2中具有种系致病变异体(gPV)的个体患乳腺癌和可能的其他原发性癌症的风险增加。PARP抑制剂（PARPi）已被证明可有效治疗HRR缺乏的癌症。例如由BRCA1/2失活引起的。然而,临床试验显示,PARPi对CHEK2gPV患者几乎没有疗效.这里,我们表明,CHEK2双等位基因gPV(种系CHEK2缺乏症)患者的乳腺癌和非乳腺癌均未出现符合HRR缺乏症的分子谱.这一发现提供了一个可能的解释，为什么PARPi疗法不能成功治疗CHEK2缺陷型癌症。
