China
Africa
Explore chapters and articles related to this topic
Nanomaterials for Theranostics: Recent Advances and Future Challenges *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Eun-Kyung Lim, Taekhoon Kim, Soonmyung Paik, Seungjoo Haam, Yong-Min Huh, Kwangyeol Lee
Tyrosine kinases that are responsible for activation of signal transduction cascades can be inhibited by tyrosine kinase inhibitors. These are used as anticancer drugs by competing with ATP [211]. About 15%–20% of patients with early-stage breast cancer have tumors that overexpress or amplify HER2 genes, which is associated with increased proliferation of cancer cells and poor prognosis [390–394]. When HER2 binds to the ligands (preferably forming dimers), the HER2 pathway can initiate the mitogen-activated protein kinase pathway as well as the PI3K/Akt pathway, which in turn activates the nuclear factor kappa B pathway. When growth factors bind to their receptors on the cell surface, the receptors give a signal causing cell division. However, if growth factor receptor inhibitors bind to their receptors, the receptors no longer cause uncontrolled cell proliferation. Trastuzumab (Herceptin) is a HER2-specific mAb and the only approved HER2-targeted drug. Cells targeted with trastuzumab experience cell cycle arrest in the G phase; thus, cell proliferation is reduced by downregulation of HER2/neu [383, 384]. When cancer develops it requires generation of neovasculature for nutrient and oxygen supply. Trastuzumab suppresses angiogenesis, formation of new blood vessels, by both induction of antiangiogenic factors and repression of proangiogenic factors. Cetuximab (Erbitux), an EGFR inhibitor, binds to EGFR and inhibits uncontrolled growth of cancers with EGFR mutations [215, 216, 395–400].
Endocrine and Neuroendocrine Tumors
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Natasha Shrikrishnapalasuriyar, P.N. Plowman, Márta Korbonits, Ashley B. Grossman
RET is a transmembrane receptor protein-tyrosine kinase that is required for the development of the nervous system/neural crest and several other tissues. The mechanism of activation of RET by its glial-cell derived neurotrophic factor (GDNF) ligands requires additional GDNF family receptor-α (GFRα) co-receptors (GFRα1/2/3/4). RET point mutations have been reported in multiple endocrine neoplasia (MEN2A, MEN2B) and medullary thyroid carcinoma. RET fusion proteins have been reported in papillary thyroid and non-small cell lung adenocarcinomas. There has been much recent interest and clinical benefit from the use of the RET inhibitors in the therapy of metastatic medullary thyroid cancer. Vandetanib and cabozantinib have been licensed and are of proven efficacy; recently, a more potent agent, Blue-667, has become available and looks more promising still. This last drug has activity in the brain (of more importance in the RET-driven lung cancers than medullary carcinoma of thyroid). Side-effects such as hypertension, ECG changes, and blood test abnormalities are usually minor but close monitoring is required—as for all cancer patients on tyrosine kinase inhibitors.
Endothelial Cell Signaling During Wound Healing
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
The experiments described above were designed to define the role and mechanisms of tyrosine phosphorylation events during endothelial cell wound healing. We have employed specific tyrosine kinase inhibitors with two different mechanisms of action to probe these issues. We have previously demonstrated herbimycin A inhibition of focal adhesion formation, and stress fiber assembly in REF52, NIH 3T3 and Balb/c 3T3 cells68,69 in a pattern similar to that seen in tyrphostin-treated HUVEC, VEC, and REF52 (see Figures 6 and 7, above). The fact that both herbimycin A and tyrphostins also inhibited FAK activity and endothelial cell wound healing42 suggests that it is the inhibition of tyrosine kinase activity, rather than any other effect of these agents, that accounts for these observations. These agents were chosen in part for their specificity. Tyrphostins are competitive tyrosine kinase inhibitors80 that have been shown to have no effect on the activity of serine and threonine kinases.89 Herbimycin A has proven a potent inhibitor of Src-family tyrosine kinases, while it did not alter the activity of other oncogene products including raf, ras, or myc.90 The specificities of these agents contrast with the range of specificity reported for other tyrosine kinase inhibitors such as genistein and erbstatin that also inhibit protein kinases A and C.91,92
Novel topoisomerase II/EGFR dual inhibitors: design, synthesis and docking studies of naphtho[2′,3′:4,5]thiazolo[3,2-a]pyrimidine hybrids as potential anticancer agents with apoptosis inducing activity
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Mai A. E. Mourad, Ayman Abo Elmaaty, Islam Zaki, Ahmed A. E. Mourad, Amal Hofni, Ahmed E. Khodir, Esam M. Aboubakr, Ahmed Elkamhawy, Eun Joo Roh, Ahmed A. Al-Karmalawy
Of considerable interest, protein tyrosine kinases are considered one of the most important protein families that contribute to many diseases, particularly cancer, as they are involved in almost every aspect of the cellular processes22. Among them, epidermal growth factor receptor (EGFR) which plays a key role in cell proliferation, survival, growth, angiogenesis, differentiation and metastasis23. It is over-expressed in a significant number of human tumours specifically non-small cell lung cancer (NSCLC) and breast cancer24. In view of this, targeting EGFR is considered an efficient goal for the development of new anti-cancer agents that inhibit tumour angiogenesis and consequently tumour growth. Several EGFR inhibitors have been reported, including the Food and Drug Administration (FDA)-approved erlotinib, lapatinib and gefitinib25,26 (Figure 2).
BRAF testing in a South African cohort of MLH1 deficient endometrial carcinomas: lessons learnt
Published in Southern African Journal of Gynaecological Oncology, 2021
BRAF is a subtype of RAF protein that has serine-threonine kinase activity, and forms part of the RAS/RAF/MAP/ERK pathway that culminates in cell proliferation.1 Activity of RAF is usually under control of RAS. Constitutive activation of the RAS/RAF/MAP/ERK pathway occurs due to mutations in BRAF V600E, resulting in carcinogenesis. Studies have shown that BRAF V600E codon mutations result in ten times the tyrosine kinase activity in contrast to wild-type BRAF.2 Tyrosine kinases are involved in cellular communication and assist in the regulation of cell growth and differentiation of cells. Thus, tyrosine kinase dysregulation culminates in an assortment of disorders, in particular neoplasia.3 The role of BRAF mutations in tumours such as malignant melanomas and colorectal carcinomas is well established and such mutations are identified in up to half of colonic carcinomas.4 The presence of MLH1 promoter hypermethylation, as well as mutations in BRAF V600E, suggests sporadic occurrence of a colorectal neoplasm.5
Unveiling Taenia solium kinome profile and its potential for new therapeutic targets
Published in Expert Review of Proteomics, 2020
Naina Arora, Anand Raj, Farhan Anjum, Rimanpreet Kaur, Suraj Singh Rawat, Rajiv Kumar, Shweta Tripathi, Gagandeep Singh, Amit Prasad
Tyrosine kinases are classified as receptor tyrosine kinase and cytoplasmic tyrosine kinase based on the presence or absence of transmembrane domains. It is the third most abundant kinase in T. solium with 34 sequences; representing six receptor kinase families and nine cytoplasmic kinase families (supplementary 7). The receptor tyrosine kinases are involved in transmembrane signaling; the signaling is mediated by three domains present: extracellular domain, transmembrane domain, and an intracellular domain which carries catalytic center. On ligand binding, the receptor dimerizes and undergoes conformational change that relays signaling. This class consists of EGFR, FGFR, InsR, etc., which participate in growth, development, and metabolism [53]. On the contrary, cytoplasmic tyrosine kinases are involved in signaling to nucleus.