The Kinghorn Cancer Centre, The Garvan Institute of Medical Research, Sydney, Australia.
Faculty of Medicine, St Vincent's Clinical School, University of NSW, Sydney, Australia.
FEBS J. 2019 Sep;286(18):3510-3539. doi: 10.1111/febs.15011. Epub 2019 Aug 5.
Pancreatic cancer, a disease with extremely poor prognosis, has been notoriously resistant to virtually all forms of treatment. The dynamic crosstalk that occurs between tumour cells and the surrounding stroma, frequently mediated by intricate Src/FAK signalling, is increasingly recognised as a key player in pancreatic tumourigenesis, disease progression and therapeutic resistance. These important cues are fundamental for defining the invasive potential of pancreatic tumours, and several components of the Src and downstream effector signalling have been proposed as potent anticancer therapeutic targets. Consequently, numerous agents that block this complex network are being extensively investigated as potential antiinvasive and antimetastatic therapeutic agents for this disease. In this review, we will discuss the latest evidence of Src signalling in PDAC progression, fibrotic response and resistance to therapy. We will examine future opportunities for the development and implementation of more effective combination regimens, targeting key components of the oncogenic Src signalling axis, and in the context of a precision medicine-guided approach.
胰腺癌预后极差，几乎对所有形式的治疗都具有耐药性。肿瘤细胞与周围基质之间的动态串扰，通常由复杂的Src/FAK 信号介导，越来越被认为是胰腺癌发生、疾病进展和治疗耐药的关键因素。这些重要线索对于定义胰腺肿瘤的侵袭潜力至关重要，Src 和下游效应子信号的几个成分已被提议作为有效的抗癌治疗靶点。因此，许多阻断该复杂网络的药物正被广泛研究，作为该疾病潜在的抗侵袭和抗转移治疗药物。在这篇综述中，我们将讨论 Src 信号在 PDAC 进展、纤维化反应和治疗耐药性中的最新证据。我们将探讨针对致癌 Src 信号轴的关键成分，开发和实施更有效的联合治疗方案的未来机会，并在精准医学指导的方法背景下进行探讨。
