Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan.
Everfront Biotech Inc., New Taipei City 221, Taiwan.
Int J Mol Sci. 2021 Jul 29;22(15):8125. doi: 10.3390/ijms22158125.
Despite the improved overall survival rates in most cancers, pancreatic cancer remains one of the deadliest cancers in this decade. The rigid microenvironment, which majorly comprises cancer-associated fibroblasts (CAFs), plays an important role in the obstruction of pancreatic cancer therapy. To overcome this predicament, the signaling of receptor tyrosine kinases (RTKs) and TGF beta receptor (TGFβR) in both pancreatic cancer cell and supporting CAF should be considered as the therapeutic target. The activation of receptors has been reported to be aberrant to cell cycle regulation, and signal transduction pathways, such as growth-factor induced proliferation, and can also influence the apoptotic sensitivity of tumor cells. In this article, the regulation of RTKs/TGFβR between pancreatic ductal adenocarcinoma (PDAC) and CAFs, as well as the RTKs/TGFβR inhibitor-based clinical trials on pancreatic cancer are reviewed.
尽管大多数癌症的总体存活率有所提高，但在这十年中，胰腺癌仍是最致命的癌症之一。刚性微环境主要由癌相关成纤维细胞（CAF）组成，在胰腺癌治疗的阻碍中起着重要作用。为了克服这一困境，应将受体酪氨酸激酶（RTKs）和转化生长因子β受体（TGFβR）在胰腺癌细胞和支持 CAF 中的信号传导视为治疗靶标。据报道，受体的激活与细胞周期调控和信号转导途径（如生长因子诱导的增殖）异常相关，也会影响肿瘤细胞的凋亡敏感性。本文综述了胰腺导管腺癌（PDAC）和 CAF 之间 RTKs/TGFβR 的调节，以及基于 RTKs/TGFβR 抑制剂的胰腺癌临床试验。
