Mutational Analysis of the Tyrosine Kinome in Colorectal Cancers

  title={Mutational Analysis of the Tyrosine Kinome in Colorectal Cancers},
  author={Alberto Bardelli and D. Williams Parsons and Natalie Silliman and Janine Ptak and Steve Szabo and Saurabh Saha and Sanford D. Markowitz and James K. V. Willson and Giovanni Parmigiani and Kenneth W. Kinzler and Bert Vogelstein and Victor E. Velculescu},
  pages={949 - 949}
Tyrosine kinases (TKs) are central regulators of signaling pathways that control differentiation, transcription, cell cycle progression, apoptosis, motility, and invasion ( [1][1] ). Although a few TK genes have been shown to be mutationally altered in specific human cancers ( [1][1] ), it is not 
Colorectal cancer: Mutations in a signalling pathway
Analysis of human colorectal cancers for genetic mutations in 340 serine/threonine kinases found mutations in eight genes, including three members of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway, which may provide new targets for therapeutic intervention.
The Role of Janus Kinases in Hematopoietic Malignancies
The somatic mutations in the Janus family kinases are reviewed and the associated hematological phenotypes associated with overproduction of terminally differentiated cells and/or blastic transformation are reviewed.
Effects of Tropomyosin-Related Kinase A Inhibitors on the Proliferation of Human Lung Cancer Cells
The tropomyosin-related kinases (Trks), which play acritical role in the development and maintenance of the central and peripheral nervous systems, are included in this small kinase subfamily.
Mutational Analysis of the Tyrosine Phosphatome in Colorectal Cancers
Observations suggest that the mutated tyrosine phosphatases are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.
Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers
The results implicate these tyrosine kinase genes in the pathogenesis of other tumor types and suggest that they may be useful targets for diagnostic and therapeutic intervention in selected patients.
No mutations in the tyrosine kinases of human hepatic, pancreatic, and gastric cancer cell lines
No tyrosine kinase-gene mutations were found in any of the 22 hepatic, pancreatic, and gastric cancer cell lines examined, indicating marked differences in the oncogenesis or cancer progression mechanisms may exist between colorectal cancer and hepatic and pancreatic cancers.
Control of Tyrosine Kinase Signalling by Small Adaptors in Colorectal Cancer
How the Src-like adaptor protein (SLAP) and the suppressor of cytokine signalling (SOCS) adaptor proteins regulate the SRC and the Janus kinase (JAK) oncogenic pathways are reviewed and how their loss of function in the intestinal epithelium may influence tumour formation are discussed.
Roles of TrkC Signaling in the Regulation of Tumorigenicity and Metastasis of Cancer
  • W. Jin
  • Medicine, Biology
  • 2020
It is demonstrated that Trk inhibitors were highly effective in inducing tumor regression in patients who do not harbor mutations in the kinase domain, and next-generation Trk inhibitor have been developed and are currently under investigation in clinical trials.
Functions of Fibroblast Growth Factor Receptors in cancer defined by novel translocations and mutations.
The effects of genetic alterations in Fibroblast Growth Factor Receptors on downstream signaling cascades, and the challenge of drug resistance in cancer treatment with antagonists of FGFRs are discussed.
The regulatory function of mixed lineage kinase 3 in tumor and host immunity.
How Mixed Lineage Kinase 3 regulates different MAPK pathways, cancer cell growth and survival, apoptosis, and host's immunity is described and how MLK3 inhibitors can potentially be used along with immunotherapy for different malignancies are discussed.


Oncogenic kinase signalling
How oncogenic conversion of protein kinases results from perturbation of the normal autoinhibitory constraints on kinase activity is emphasized and an update is provided on the role of deregulated PI(3)K/Akt and mammalian target of rapamycin/p70S6K signalling in human malignancies.
Perspectives on the development of a molecularly targeted agent.
The identification of Bcr-Abl as a therapeutic target in chronic myelogenous leukemia and the steps in the development of an agent to specifically inactivate this abnormality are reviewed.
The Protein Kinase Complement of the Human Genome
The protein kinase complement of the human genome is catalogued using public and proprietary genomic, complementary DNA, and expressed sequence tag sequences to provide a starting point for comprehensive analysis of protein phosphorylation in normal and disease states and a detailed view of the current state of human genome analysis through a focus on one large gene family.