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Published on: February 17, 2019
Is Src a viable target for treating solid tumours?
B Elsberger1, B Stewart, O Tatarov
1Glasgow Western Infirmary, Section of Surgery, Division of Cancer Sciences and Molecular Pathology, Faculty of Medicine, Level 2, McGregor Building, Dumbarton Road, Glasgow G11 0NT, Scotland, UK.
Abstract:
Src was the first proto-oncogene to be discovered. Since then the role of Src has been extensively studied in vitro. Src is a key regulator of multiple signal transduction pathways and plays a significant part in cellular transformation. Dysfunction of Src, through overexpression or increased activation, has profound effects on basic cellular functions. Elevated Src expression and/or activation is evident across a wide range of solid tumour types, highlighting its place in carcinogenesis and making it an attractive therapeutic target. In this review, we discuss in vitro and in vivo data examining the role of Src in the different cellular processes involved in oncogenesis and metastasis, covering the association of Src with increased cell proliferation and survival, decreased cellular adhesion, increased cell motility and invasiveness, accelerated/advanced angiogenesis and pathogenic bone activity. We also review evidence gathered from human tumour tissue and translational research studies that further substantiates the role of Src in oncogenesis. A summary of Src inhibitors currently being developed and trialled as therapeutic agents is provided to underline Src as a potential molecular target for solid tumour therapy. Further clinical data are needed to conclusively demonstrate that Src inhibitors have clinical utility in the treatment of solid tumors.
Insights
The proto-oncogene Src regulates cell growth and transformation. Elevated Src activity is linked to various cancers, making Src inhibitors a promising therapeutic target for solid tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Biology
Background:
- Src is the first identified proto-oncogene, crucial for cell signaling and transformation.
- Src dysfunction, via overexpression or hyperactivation, significantly impacts cellular functions.
- Elevated Src is observed in numerous solid tumors, implicating it in carcinogenesis.
Purpose of the Study:
- To review in vitro and in vivo data on Src's role in oncogenesis and metastasis.
- To examine Src's association with key cancer hallmarks.
- To summarize the therapeutic potential of Src inhibitors for solid tumors.
Main Methods:
- Review of in vitro and in vivo studies on Src function.
- Analysis of data from human tumor tissues and translational research.
- Compilation of information on current Src inhibitor development and trials.
Main Results:
- Src dysregulation contributes to increased cell proliferation, survival, motility, and invasiveness.
- Src is associated with decreased cell adhesion, enhanced angiogenesis, and bone activity.
- Evidence from human tumors and translational studies supports Src's role in oncogenesis.
Conclusions:
- Src is a significant molecular target for solid tumor therapy.
- Src inhibitors are under development and clinical trials.
- Further clinical data are required to confirm the utility of Src inhibitors in solid tumor treatment.
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