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Oncogenesis and Metastasis
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Growth factorsFunction in extrinsic control of cell cycle through signalling pathways.Examples: epidermal growth factor (EGF) and fibroblast growth factor (FGF).Bind cell surface receptors.Drive cell proliferation.
Principles of systemic treatment
Published in Peter Hoskin, Peter Ostler, Clinical Oncology, 2020
Communication within and between cells is mediated by extensive biochemical interactions triggered by cell surface receptors. Tyrosine kinases are frequent components of these cascades, particularly those related to the epidermal growth control receptor (EGFR) and angiogenesis (VEGF [vascular endothelial growth factor] and PDGF [platelet-derived growth factor]). Drugs which act primarily through the inhibition of tyrosine kinases include imatinib, gefitinib, sorafenib and sunitinib.
Tissue injury and repair
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
The control of cell division and regulation of the cell cycle are discussed in Chapter 2. In broad terms, cell proliferation is controlled by the binding of extracellular growth factors to specific receptors on the surface of the cells. Ligand−receptor binding, in turn, sets in motion a series of cascade processes or signal transduction pathways by which signals are transferred to the nucleus, leading to activation of transcription factors, ultimately influencing gene expression. Of importance are the changes in the expression of genes that control entry into the cell cycle. This includes several proto-oncogenes such as c-myc and tumour-suppressor genes such as TP53 (see Chapter 6). The cell surface receptors are of three types: (1) those that act through intrinsic tyrosine kinase activity, (2) transmembrane receptors without intrinsic enzyme activity, and (3) receptors linked to G proteins. There are several different forms of signal transduction pathway, which link these receptors to nuclear events. The principal pathways are the mitogen-activated protein (MAP) kinase pathway, inositol phosphate pathway, cyclic adenosine monophosphate (cAMP) pathway, the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway and integrin-mediated pathways. This is almost certainly an oversimplification and there is evidence of cross-talk between the different pathways.
High-throughput optofluidic screening of single B cells identifies novel cross-reactive antibodies as inhibitors of uPAR with antibody-dependent effector functions
Published in mAbs, 2023
André Luiz Lourenço, Shih-Wei Chuo, Markus F. Bohn, Byron Hann, Shireen Khan, Neha Yevalekar, Nitin Patel, Teddy Yang, Lina Xu, Dandan Lv, Robert Drakas, Sarah Lively, Charles S. Craik
Since suPAR lacks the cell surface anchoring motif, antibodies generated by immunizing animals with suPAR can target protein regions that are not accessible for membrane-bound uPAR. Nonetheless, effective targeting of cell surface receptors benefits from recognizing both solvent-exposed epitopes and also native conformational states displayed on the cell surface.35 Although the Beacon platform allows on-cell screening, we preferred a more quantitative methodology. Thus, we applied FACS to evaluate the cell-surface uPAR recognition by each antibody in the triple-negative breast cancer cell line, MDA-MB-231, that expresses uPAR endogenously (Figure 2). Human isotype IgG1 (hIgG1) served as a negative control, and all antibodies were benchmarked against 2G10, 3C6, and trastuzumab (Tras). The binding curves demonstrated 11 antibodies recognized cell-surface uPAR in a dose-dependent manner and are comparable to trastuzumab binding to HER2 (EC50 = 3.6 nM) (Table 1 and Figure 2),36,37 showing a more potent ability to recognize cell-surface uPAR than 2G10 and 3C6.
Colorectal cancer management: strategies in drug delivery
Published in Expert Opinion on Drug Delivery, 2022
Prabha Singh, Pramita Waghambare, Tabassum Asif Khan, Abdelwahab Omri
Targeted drug delivery systems, sometimes called smart drug delivery systems, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body compared to others. Targeted therapies are generally better tolerated than traditional chemotherapy as targeted receptors can be either tumor specific or tissue specific [68]. Cell surface receptors and their cognate ligands provide unique opportunities for specific delivery of drugs. Basic targeting is achieved by a specific interaction between the drug and its receptor (Figure 4, Table 5) [69]. In CRC, many proteins are overexpressed during tumor progression and targeting these specific proteins can minimize the toxicity to normal tissues [70]. Table 6 depicts the targeting ligands and anti-cancer drugs with their mechanism of action.
Safety of EGFR-TKIs for EGFR mutation-positive non-small cell lung cancer
Published in Expert Opinion on Drug Safety, 2020
Jia-Ying Zhou, Si-Yang Liu, Yi-Long Wu
Cell-surface receptors regulate cell proliferation, apoptosis, adhesion and movement, as well as tumor angiogenesis, thereby affecting tumor growth and progression. EGFR tyrosine kinases (TKs) belong to the family of cell-surface receptors. In normal cells, the TK activity of EGFR is tightly controlled, but in malignant cells, genes encoding these receptors may escape normal intracellular inhibition mechanisms [4].The mechanism of action of first-generation EGFR-TKIs, such as gefitinib and erlotinib, involves inhibition of EGFR signaling through reversible binding, while second-generation EGFR-TKI, afatinib and dacomitinib irreversibly block the signaling of all homodimers and heterodimers in the ErbB receptor family (EGFR/ErbB1, HER2/ErbB2, ErbB3, and ErbB4) [5,6]. However, approximately 60% of patients develop a p.Thr790 Met point mutation (T790 M) in the gene encoding EGFR during disease progression, which induces resistance to both first- and second-generation EGFR-TKIs [7]. Third-generation TKI agents, such as osimertinib, can overcome the resistance induced by T790 M and also can be applied in patients of NSCLC with other EGFR mutations (e.g., 19Del and 21L858 R) [5,7]