Biomedica Molecular Medicine SL, Madrid, Spain.
Molecular Oncology and Pathology Lab, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
Sci Rep. 2021 Apr 1;11(1):7402. doi: 10.1038/s41598-021-86966-w.
Squamous cell carcinoma is the most frequent histologic type of anal carcinoma. The standard of care since the 1970s has been a combination of 5-fluorouracil, mitomycin C, and radiotherapy. This treatment is very effective in T1/T2 tumors (achieving complete regression in 80-90% of tumors). However, in T3/T4 tumors, the 3-year relapse free survival rate is only 50%. The VITAL trial aimed to assess the efficacy and safety of panitumumab in combination with this standard treatment. In this study, 27 paraffin-embedded samples from the VITAL trial and 18 samples from patients from daily clinical practice were analyzed by whole-exome sequencing and the influence of the presence of genetic variants in the response to panitumumab was studied. Having a moderate- or high-impact genetic variant in PIK3CA seemed to be related to the response to panitumumab. Furthermore, copy number variants in FGFR3, GRB2 and JAK1 were also related to the response to panitumumab. These genetic alterations have also been studied in the cohort of patients from daily clinical practice (not treated with panitumumab) and they did not have a predictive value. Therefore, in this study, a collection of genetic alterations related to the response with panitumumab was described. These results could be useful for patient stratification in new anti-EGFR clinical trials.
鳞状细胞癌是肛门癌最常见的组织学类型。自 20 世纪 70 年代以来，标准治疗方法一直是氟尿嘧啶、丝裂霉素 C 和放疗的联合治疗。这种治疗方法在 T1/T2 肿瘤中非常有效（80-90%的肿瘤完全消退）。然而，在 T3/T4 肿瘤中，3 年无复发生存率仅为 50%。VITAL 试验旨在评估帕尼单抗联合标准治疗的疗效和安全性。在这项研究中，对来自 VITAL 试验的 27 个石蜡包埋样本和来自日常临床实践的 18 个样本进行了全外显子组测序分析，并研究了遗传变异对帕尼单抗反应的影响。PIK3CA 中存在中度或高度影响的遗传变异似乎与帕尼单抗的反应有关。此外，FGFR3、GRB2 和 JAK1 的拷贝数变异也与帕尼单抗的反应有关。这些遗传改变也在来自日常临床实践（未用帕尼单抗治疗）的患者队列中进行了研究，但它们没有预测价值。因此，在这项研究中，描述了一组与帕尼单抗反应相关的遗传改变。这些结果可能有助于在新的抗 EGFR 临床试验中对患者进行分层。
