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Published on: January 7, 2019
The stem cell factor receptor/c-Kit as a drug target in cancer
1Ludwig Institute for Cancer Research, Uppsala University, Box 595, SE-751 24 Uppsala, and Department of Laboratory Medicine, Lund University, Malmö University Hospital, Sweden.
Abstract:
Tyrosine phosphorylation has a key role in intracellular signaling. Inappropriate proliferation and survival cues in tumor cells often occur as a consequence of unregulated tyrosine kinase activity. Much of the current development of anti-cancer therapies tries to target causative proteins in a specific manner to minimize side-effects. One attractive group of target proteins is the kinases. c-Kit is a receptor tyrosine kinase that normally controls the function of primitive hematopoietic cells, melanocytes and germ cells. It has become clear that uncontrolled activity of c-Kit contributes to formation of an array of human tumors. The unregulated activity of c-Kit may be due to overexpression, autocrine loops or mutational activation. This makes c-Kit an excellent target for cancer therapies in these tumors. In this review we will highlight the current knowledge on the signal transduction molecules and pathways activated by c-Kit under normal conditions and in cancer cells, and the role of aberrant c-Kit signaling in cancer progression. Recent advances in the development of specific inhibitors interfering with these signal transduction pathways will be discussed.
Insights
Uncontrolled c-Kit tyrosine kinase activity drives tumor growth. This review explores c-Kit signaling in cancer and discusses targeted therapies, including new inhibitors, for effective anti-cancer treatments.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tyrosine phosphorylation is crucial for cell signaling.
- Aberrant tyrosine kinase activity, particularly c-Kit, drives tumor cell proliferation and survival.
- c-Kit receptor tyrosine kinase dysregulation is implicated in various human cancers.
Purpose of the Study:
- To review the role of c-Kit signaling in normal cell function and cancer.
- To highlight the mechanisms of c-Kit dysregulation in tumorigenesis.
- To discuss advancements in c-Kit-targeted cancer therapies.
Main Methods:
- Literature review of c-Kit signaling pathways.
- Analysis of c-Kit's role in normal physiology and oncogenesis.
- Summary of current and emerging c-Kit inhibitor strategies.
Main Results:
- c-Kit signaling pathways are complex, involving multiple downstream effectors.
- Aberrant c-Kit activation (overexpression, mutations, autocrine loops) promotes cancer progression.
- Specific inhibitors targeting c-Kit signaling show promise in preclinical and clinical settings.
Conclusions:
- c-Kit is a validated therapeutic target in multiple tumor types.
- Targeting c-Kit signaling offers a promising strategy for cancer treatment.
- Continued research into c-Kit pathways and inhibitors is essential for improving patient outcomes.
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