Molecular Diagnostics and Pharmacogenetics Unit, IRCCS Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy.
Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, 70124 Bari, Italy.
Medicina (Kaunas). 2021 Nov 13;57(11):1241. doi: 10.3390/medicina57111241.
Colorectal cancer (CRC) is one of the most common cancer types around the world. The prognosis of patients with advanced diseases is still poor in spite of currently available therapeutic options. Regorafenib is an oral tyrosine kinase inhibitor (TKI) approved to treat refractory metastatic colorectal cancer (mCRC). We investigated Somatic mutations in several genes involved in immunological response and cancer progression in both long/short responder mCRC patients who underwent third-line therapy with regorafenib to identify predictive biomarkers of response using Ion Torrent PGM sequencing and bioinformatic tools. We found Somatic mutations in TGFBR1, TGFBR2, and TGFBR3 genes in primary tumor and metastases samples of long-responder patients. Furthermore, our bioinformatic results show that they were mainly enriched in immune response, cell junction, and cell adhesion in long responder patients, particularly in primary tumor and metastatic sites. These data suggest that the TGF-b pattern could be the leading actor of a prolonged response to this drug.
结直肠癌（CRC）是全球最常见的癌症类型之一。尽管目前有多种治疗选择，但晚期患者的预后仍然较差。regorafenib 是一种口服酪氨酸激酶抑制剂（TKI），被批准用于治疗难治性转移性结直肠癌（mCRC）。我们在接受regorafenib 三线治疗的长/短反应 mCRC 患者的原发肿瘤和转移样本中研究了几个参与免疫反应和癌症进展的基因的体细胞突变，以使用 Ion Torrent PGM 测序和生物信息学工具识别反应的预测生物标志物。我们发现长反应患者的原发肿瘤和转移样本中存在 TGFBR1、TGFBR2 和 TGFBR3 基因的体细胞突变。此外，我们的生物信息学结果表明，它们主要富集在长反应患者的免疫反应、细胞连接和细胞黏附通路中，特别是在原发肿瘤和转移部位。这些数据表明，TGF-b 模式可能是对这种药物产生持久反应的主导因素。
