colorectal neoplasms/tyrosine

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BRAF inhibition upregulates a variety of receptor tyrosine kinases and their downstream effector Gab2 in colorectal cancer cell lines.

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BRAF mutations occur in ~10% of colorectal cancer (CRC) and are associated with poor prognosis. Inhibitors selective for the BRAFV600E oncoprotein, the most common BRAF mutant, elicit only poor response rates in BRAF-mutant CRC as single agents. This unresponsiveness was mechanistically attributed

Overexpression of SAP-1, a transmembrane-type protein tyrosine phosphatase, in human colorectal cancers.

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SAP-1 is a human transmembrane-type protein tyrosine phosphatase that is abundant in colon and pancreatic cancer cell lines. The expression of SAP-1 in surgically excised human colorectal cancer specimens has now been investigated by immunohistochemical staining and in situ hybridization. Normal

Absence of tyrosine kinase mutations in Japanese colorectal cancer patients.

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Tyrosine kinases, which are important regulators of intracellular signal-transduction pathways, have mutated forms that are often associated with oncogenesis and are attractive targets for therapeutic intervention. Recently, systematic mutational analyses of tyrosine kinases revealed that a minimum

Functional Analysis of Somatic Mutations Affecting Receptor Tyrosine Kinase Family in Metastatic Colorectal Cancer.

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Besides the detection of somatic receptor tyrosine kinases (RTK) mutations in tumor samples, the current challenge is to interpret their biological relevance to give patients effective targeted treatment. By high-throughput sequencing of the 58 RTK exons of healthy tissues, colorectal tumors, and

Control of Tyrosine Kinase Signalling by Small Adaptors in Colorectal Cancer.

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Tyrosine kinases (TKs) phosphorylate proteins on tyrosine residues as an intracellular signalling mechanism to coordinate intestinal epithelial cell communication and fate decision. Deregulation of their activity is ultimately connected with carcinogenesis. In colorectal cancer (CRC), it is still

A phase I pharmacokinetic study of TSU-68 (a multiple tyrosine kinase inhibitor of VEGFR-2, FGF and PDFG) in combination with S-1 and oxaliplatin in metastatic colorectal cancer patients previously treated with chemotherapy.

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TSU-68 is a novel multiple tyrosine kinase inhibitor that inhibits VEGFR-2, FGF and PDGF receptors. We conducted a phase I study to evaluate the safety and pharmacokinetic of TSU-68 when used with S-1 and oxaliplatin (SOX) in metastatic colorectal cancer (mCRC) patients. Patients with mCRC were

Responses of human colorectal tumor cells to treatment with the anti-epidermal growth factor receptor monoclonal antibody ICR62 used alone and in combination with the EGFR tyrosine kinase inhibitor gefitinib.

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The anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab has been approved for the treatment of patients with metastatic colorectal cancer. However, there is currently no reliable marker for response to therapy with the EGFR inhibitors. In this study, we investigated the

Failure of detection of the tyrosine to histidine substitution at the residue 33 of thymidylate synthase in human colorectal cancer. A preliminary study.

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Structural changes in the macromolecular targets of pharmacological agents can result in alterations in the efficacy of these agents. In previous studies Berger et al. (1) identified a variant structural form of thymidylate synthase (TS) that is associated with relative resistance to

Antiangiogenic tyrosine kinase inhibitors in colorectal cancer: is there a path to making them more effective?

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Antiangiogenic therapy has a proven survival benefit in metastatic colorectal cancer. Inhibition of the VEGF pathway using a variety of extracellular antibody approaches has clear benefit in combination with chemotherapy, while intracellular blockade using tyrosine kinase inhibitors (TKIs) such as

A phase Ib study of linsitinib (OSI-906), a dual inhibitor of IGF-1R and IR tyrosine kinase, in combination with everolimus as treatment for patients with refractory metastatic colorectal cancer.

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OBJECTIVE To determine the maximum tolerated dose (MTD) of the combination of linsitinib (OSI-906), a dual inhibitor of IGFR and IR tyrosine kinase activity, and everolimus as treatment for patients with refractory metastatic colorectal cancer (mCRC). METHODS Eligible adult patients with refractory

Vascular endothelial growth factor receptor tyrosine kinase inhibitors versus bevacizumab in metastatic colorectal cancer: A systematic review and meta-analysis.

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Bevacizumab has demonstrated a survival benefit in patients with metastatic colorectal cancer (mCRC) when combined with chemotherapy. Several randomized clinical trials comparing the efficacy and toxicity of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs)

Combined expression of the non-receptor protein tyrosine kinases FAK and Src in primary colorectal cancer is associated with tumor recurrence and metastasis formation.

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OBJECTIVE The protein tyrosine kinase focal adhesion kinase (FAK) and Src in association with phosphorylation of the adapter protein paxillin are essential in tumor metastasis formation. Elevated levels of FAK, Src and paxillin may increase the metastatic potential of colorectal tumor cells. The aim

The human epidermal growth factor receptor (EGFR) gene in European patients with advanced colorectal cancer harbors infrequent mutations in its tyrosine kinase domain.

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BACKGROUND The epidermal growth factor receptor (EGFR), a member of the ErbB family of receptors, is a transmembrane tyrosine kinase (TK) activated by the binding of extracellular ligands of the EGF-family and involved in triggering the MAPK signaling pathway, which leads to cell proliferation.

The role of protein tyrosine phosphatases in colorectal cancer.

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Colorectal cancer is one of the most common oncogenic diseases in the Western world. Several cancer associated cellular pathways have been identified, in which protein phosphorylation and dephosphorylation, especially on tyrosine residues, are one of most abundant regulatory mechanisms. The balance

Synergistic interaction between the EGFR tyrosine kinase inhibitor gefitinib ("Iressa") and the DNA topoisomerase I inhibitor CPT-11 (irinotecan) in human colorectal cancer cells.

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Epidermal growth factor receptor [EGFR (HER1, erbB1)] is a receptor with associated tyrosine kinase activity, and is expressed in colorectal cancers and many other solid tumors. We examined the effect of the selective EGFR tyrosine kinase inhibitor (EGFR-TKI) gefitinib ("Iressa") in combination with

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