Pdh326 Case Study

The kinase enzymes are specifically phosphorylate tyrosine amino acids, (RTKs) with similar homology; HER1, HER2, HER3, and HER4, has known as an oncogene which guided to the development of anticancer treatment directed against them (termed as "HER inhibitors") (Moulder et al., 2008). RTKs are regulators of normal cellular processes and have a critical role in the progression and development of many types of cancer. RTKs transfer extracellular signals influence cancer cell growth, survival, and differentiation. These proteins are localized to the cell membrane and contain an extracellular domain that is the site for ligand binding, a transmembrane domain, and a kinase domain that contains the ATP-binding site necessary for protein phosphorylation. RTKs phosphorylate some downstream proteins, which lead to the activation of signaling cascades such as phosphatidylinositol-3-OH kinase (PI3K) pathways. The HER family of receptors are targeted for treatment of breast cancer (Moulder et al., 2008; Paez et al.,

Imatinib is a Abl/c-kit/PDGFR inhibitor. Abl is a proto-oncogene related with chronic myelogenous leukemia. c-kit is a protein on the surface of various types of cells. PDGFR is a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor family.

When cancer forms, your body has ways of trying to stop it from further developing. The four regulators are known as proto-oncogenes (which when mutated are known as oncogenes), tumor suppressor genes, apoptosis, and telomerase genes. When there is a mutation in each of the genes, cancer can develop. Once cancer develops it continues to grow and divide and turn into a tumor. For a tumor to develop it essentially needs something supplying it with blood and nutrients so that it can continue to grow. One player in the game of supplying the tumor with blood is a protein kinase known as Protein kinase C. A protein kinase is simply a molecule that regulates numerous cellular responses including gene expression, protein secretion, cell proliferation, and the inflammatory response. According to researchers at Harvard University, EBC-46 has the ability to target protein kinase C and inhibit it, which in turn causes the tumor to die because it is no longer has the ability to synthesize proteins it needs to survive. According to the Queensland Institute, the inhibition of  protein kinase C helps destroy the blood vessels that supply the tumor with the oxygen and the nutrients it would need for survival. Pretty exciting stuff

Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK. Anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) is a molecular subtype of NSCLC with at least 27 ALK-fusion variants identified. c-Met is the prototypic member of RTKs, which is the only known high-affinity receptor for hepatocyte growth factor (HGF). Binding of HGF to the c-Met results in receptor multimerization and phosphorylation of multiple tyrosine residues at the intracellular region.

MET receptor tyrosine kinase with its ligand can promote cell survival, proliferation, and invasion. The activation of MET signaling is a common hallmark of various human cancer types, and thus, inhibition of MET signaling is an promising therapeutic opportunity for the treatment of cancer.

NE10790 is a phosphonocarboxylate analogue of the more potent bisphosphonate risedronate (BP RIS), and contains a carboxylate group instead of a phosphonate group. NE10790 is a specific inhibitor of RGGT, whereas BPs are non-specific inhibitors of Rab prenylation. They act on farnesyl diphosphate synthase to inhibit prenylation of a variety of proteins such as Rho and Ras, seen in Figure 9 (Gong, Altman and Klein, 2011). The use of BPs in clinical trials has been successful in decreasing mortality from lytic bone disease in multiple myeloma. There is also evidence of anti-tumour effects, such as apoptosis and arresting the cell cycle, as well as in other tumour cell types associated with bone. BPs have also been investigated in vitro on breast and prostate cancers, as they commonly metastasise to bone. Studies show inhibition of invasion and adhesion to bone,

The EGFR is a strong biomarker candidate for multiple reasons. First, it is overexpressed in most of the NSCLC tumours. This overexpression, ultimately is causing increased proliferation or cell motility, and decreased apoptosis, leading to the progression of the tumour(27). Another appealing reason is the fact that new approved therapies for those cancers are targeting EGFR, based on the inhibition of its TK activity(12). In addition, it is known that a portion of the membrane receptor is shed into the bloodstream(28), thus making plasma or serum an

about 2months .The plan of treatment in this work was basedon the preoperative clinical and imaging findings, together

In vitro: Previous study found that AG-370 inhibited PDGF receptor autophosphorylation and the tyrosine phosphorylation of intracellular protein substrates that coprecipitated with the PDGF receptor in digitonin-permeabilized

In vitro: IRAK-1-4 Inhibitor I was an analog of an IRAK-4 inhibitor, which was screened out from a small molecule library against IRAK-4. IRAK-1-4 Inhibitor I had a higher potency than other analogs. IRAK-1-4 Inhibitor was profiled for selectivity against other kinases. Results showed that

The JAK/STAT signaling pathway has three main components: receptor, JAK, and STAT. The receptor is on the cell surface waiting for a specific signals or ligands that fit into it. JAK stands for Janus kinase, Janus is the Greek word for god of transition and kinase is any type of enzymes that phosphorylate, giving energy by adding phosphate group, any type of proteins. JAK contains JAK tyrosine kinases which are the enzymes that can convey a phosphate group from adenosine triphosphate (ATP) to another protein. There are four different types of JAK proteins: Tyk2 (Tyrosine kinase 2), JAK 1, JAK2, and JAK3. STAT stands for signal transducers and activator of transcription and it carries

c-SRC, or also known as the proto-oncogene, is a non-receptor tyrosine kinase (nRTK). nRTKs most important function is the transfer of phosphate groups. Src is activated by many different interactions, including those with RTKs, immune response receptors and cytokine receptors. In the paper, Src is activated by recruitment to the RTK EphA2. The specific roles of each SRC kinase is not very clear as a lot of them have similar functions, however, as it activates in relation to the activity of different proteins its functions are also pretty diverse. It is known to be involved with immune response, apoptosis, transformation, cell cycle progression, and gene transcription among other things.

RAS is a biochemical molecule that is constantly being researched, and new roles and functions are consistently being discovered. The three main subcategories of RAS are K-RAS, N-RAS, and H-RAS. There is also a lesser known variant known as R-RAS. They are all functionally very similar, but function at different general areas within the cell. To discuss the functionality of RAS, it is important to go over the mechanism where it usually functions at the receptor tyrosine kinases (RTKS). RTKS are a specific type of cell-surface receptor, the other major type being G-protein coupled receptors (GPCRs). There are a variety of ligands that can bind, including platelet-derived growth factors, epidermal growth factors, and insulin. The structure of an RTK consists of one hydrophobic

Imatinib mesylate is a protein tyrosine kinase (RTK) inhibitor that exhibits high specificity and potency for ABL, c-kit, and PDGF receptors, which often harbor activating mutations and are typically mutually exclusive of each other and within specific cancer types.2 The compound has been approved as a targeted chemotherapy for Philadelphia chromosome positive chronic and acute myeloid leukemia (Ph+ CML and AML), Ph+ acute lymphoblastic leukemia (ALL), platelet-derived growth factor receptor (PDGFR) aberrancy-related myelodysplastic or myeloproliferative pathologies, kit+ expressing advanced gastrointestinal stromal tumors (GIST), and for FIP1L1-PDGFRα gene fusion expressing hypereosinophilic syndrome (HES) or chronic eosinophilic leukemia (CEL).1 Imatinib is available in 100 mg and 400 mg tablets for case-dependent single agent or adjunct therapy1. Therapeutic doses range from 100 mg to 800 mg/day, depending on diagnosis, age, and hepatic function.1 The drug exhibits pH-dependent solubility in aqueous solutions (soluble at pH ≤ 5.5), varying solubility in polar protic solvents, and is immiscible in polar aprotic liquids.1

The auto phosphorylation of EGFR by EGF causes the association of Grb2 with the SH2 domain that recruits SOS-1 which is ultimately activating Raf and ERK signalling [30]. Here, ERK kinetics was broadly similar in the three cell lines examined here following stimulation by EGF, it was rapid and transient (Fig. 10F, 11F and 12F), and this could be due to the dynamics of its receptor, as upon EGF activation the EGFR undergoes rapid internalisation and degradation, thereby terminating ERK activation. Hydrolysis of GTP to GDP terminates Ras activation, and although Ras proteins have low GTPase activity, the response was transient. This may be due to negative feedback or other regulatory proteins acting as GTPase-activating proteins being activated by Ras, which in turn accelerates the hydrolysis of GTP to GDP and subsequently prevents prolonged Ras stimulation signalling [31].