Cancer Biology and Therapeutics Laboratory, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
UCD School of Biomolecular and Biomedical Science, University College Dublin, Belfield, Dublin, Ireland.
Expert Opin Ther Targets. 2022 Feb;26(2):155-169. doi: 10.1080/14728222.2022.2032652. Epub 2022 Feb 11.
The Serum Response Factor (SRF) is a transcription factor involved in three hallmarks of cancer: the promotion of cell proliferation, cell death resistance and invasion and metastasis induction. Many studies have demonstrated a leading role in the development and progression of multiple cancer types, thus highlighting the potential of SRF as a prognostic biomarker and therapeutic target, especially for cancers with poor prognosis.
This review examines the role of SRF in several cancers in promoting cellular processes associated with cancer development and progression. SRF co-factors and signaling pathways are discussed as possible targets to inhibit SRF in a tissue and cancer-specific way. Small-molecule inhibitors of SRF, such as the CCGs series of compounds and lestaurtinib, which could be used as cancer therapeutics, are also discussed.
Targeting of SRF and its co-factors represents a promising therapeutic approach. Further understanding of the molecular mechanisms behind the action of SRF could provide a pipeline of novel molecular targets and therapeutic combinations for cancer. Basket clinical trials and the use of SRF immunohistochemistry as companion diagnostics will help testing of these new targets in patients.
血清反应因子（SRF）是一种参与癌症三个标志的转录因子：促进细胞增殖、抵抗细胞死亡和诱导侵袭和转移。许多研究表明，它在多种癌症的发生和发展中起着主导作用，因此突出了 SRF 作为预后生物标志物和治疗靶点的潜力，特别是对于预后不良的癌症。
本综述探讨了 SRF 在几种癌症中促进与癌症发展和进展相关的细胞过程的作用。讨论了 SRF 的共因子和信号通路，作为以组织和癌症特异性方式抑制 SRF 的可能靶点。还讨论了 SRF 的小分子抑制剂，如 CCG 系列化合物和 lestaurtinib，它们可被用作癌症治疗药物。
靶向 SRF 及其共因子代表了一种很有前途的治疗方法。对 SRF 作用背后的分子机制的进一步理解可能为癌症提供一系列新的分子靶点和治疗组合。篮子临床试验和将 SRF 免疫组织化学用作伴随诊断将有助于在患者中测试这些新靶点。
