RAS Lab Review

The main focus of this article was to Crizotinib as an inhibitor for ALK-rearragements in the Non-Small Cell Lung Cancer (NSCLC). The drug was first developed because of the ability for a diagnostic fluorescent in situ hybridization assay to be used to detect ALK-rearranged NSCLC. Pfizer has developed this drug to inhibit ALK and MET in many cancers that are associated with mutations in these specific genes. It has recently been shown to have an effect against ROS1-rearragements in NSCLC. This article provided better insight on the heterogeneity between ALK and ROS1 rearrangements in different subtypes of NSCLC. There is also information in the research article that sheds light into the future developments for crizotinib for ALK-rearrangements and some diagnostic assays that can detect NSCLC. This drug is important to the future of cancer therapies because it targets a subtype to NSCLC and defines a molecular target for its effectiveness. It can broaden a field which involves personalized therapies

Advance downstream, changes in the tumor silencers TSC1 and TSC2 hyper initiate motioning by mTORC1 (Laplante and Sabatini 2012). This is a critical focus of P13K-Aktsignaling. Additionally, the Ras-ERK pathway is enacted by transformations in Ras, or its downstream target Raf, that reason constitutive initiation of these proteins or by inactivation of GTPase-actuating proteins (Holes, for example, NF1, that empower the hydrolysis of GTP bound to Ras, which prompt its inactivation (Cichowski,2001).

The direct binding of rituximab to CD20 can trigger low-level apoptosis of tumor cells.6 Alterations in the apoptotic pathway signaling could therefore lead to cells becoming resistant to rituximab. Rituximab-resistant cell lines have been produced through repeated exposure to the antibody. These cell lines show apoptosis resistance and lack sensitivity to multiple cytotoxic chemotherapeutic agents, including rituximab. Numerous variations of pro- and anti-apoptotic regulators in these rituximab-resistant cell lines have been described.12 The nuclear factor-kappaB (NFkB) pathway is specifically overactivated, leading to increased expression of anti-apoptotic proteins from the Bcl-2 family. These clones can then be resensitized to rituximab by simply exposing them to inhibitors of these survival pathways in

The mutation abnormally activates AKT1 kinase, allowing cells to grow and divide without control . This abnormal cell proliferation leads to the development of cancerous tumors. Although the Glu17Lys mutation has been reported in only a few types of cancer, increased activity (expression) of the AKT1 gene is found in many types of cancer (Lindhurst et al., 2011; Carpten

B. Studies reveal that when brain tumor cells have access to glucose and glutamine, the disease will progress because gliomas cells depend on glucose for growth and

Abl is known to mutate its kinase domain so that Gleevec cannot effectively inhibit it and cellular proliferation (Lovera et al., 2015). A western blot will be run to determine the extent this mutation will affect our experiment at the beginning and 4 months into our experiment. Some tumors from all three cell lines will have their cells lysed and run through the gel, which will test for both Abl and Abl-Gleevec compound, as well as a major substrate for Arg-Abl, ArgBP2.

Nusrat Epsi, MBA is a PhD student working at the Rutgers University, School of Healthcare Professional with Dr. Antonina Mitrafanova. Prior to beginning the PhD program, Nusrat worked in the Pharmaceutical Industry. She consulted on a variety of projects which involved both qualitative and quantitative analysis to achieve strategic realignments within large pharmaceutical systems. From this work she developed an interest in drug discovery and drug structure. She is currently working on designing possible targeted cancer therapy to interfere with specific AR genes for tumor growth and progression. She also had a primary interest in the invasion of bladder cancer. She is also interested studying other Hormonal carcinogenesis. For her doctoral

After decades of experience, medical research is now focusing on slowing or preventing the progression of this cancer. By learning all the biochemical pathways involved in the initiation, progression, and proliferation of cancer, scientists hope that they can find ways to change how cancer develops.

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,

Over the past few decades, researchers have made significant advancements to the treatment and detection of cancers and similar diseases. However, these treatments have certain limitations due to cancer’s ever changing entity. If even an undetectable sliver of a tumor is left, it can mutate, multiply and wreak havoc once more. Cancer patients in remission usually face this unfortunate scenario. What’s worse is that the previous treatment is consistently compromised by the cancer’s new mutations. We are constantly chasing after cancer, it has been evading us at every turn and opportunity until now.

Pancreatic cancer has been studied many times. Pancreatic Ductal Adenocarcinoma(PDAC) is a pancreatic cancer and it is the third most leading cause of death by cancer in the world. Many studies and experiments have been done to improve the poor long-time survival rate of this disease. These studies show that a mutation in KRAS show up in many cases of pancreatic cancer. KRAS is what regulates proliferation, differentiation, metabolism, and survival. Being that KRAS has been confirmed in studies of animals that it is an initiation in cancer cells, it is a great therapeutic target. But these attempts to create something to affect the initiation of pancreatic cancer have been hindered in many ways. Scientists have been looking into how greatly

Caveolin1/2 (CAV1/CAV2); 4. cyclin-dependent kinase inhibitor 2B family (CDKN2B and CDKN2B-AS1); 5. family with sequence similarity 125, member B (FAM125B); 6. FND3B; 7. growth arrest-specific 7 (GAS7); 8. glucocorticoid induced transcript 1 (GLCCI1/ICA1) [36]; 9. RAB9B, member RAS oncogene family pseudogene 1 (RAB9BP1); 10. SIX homeobox 1/6 (SIX1/SIX6); 11. solute carrier family 2 (SLC2A14/SLC2A3) and 12. transmembrane and coiled-coil domains 1 (TMCO1)

GDC-0879 is a potent, selective and orally bioavailable RAF small-molecule inhibitor. GDC-0879 effectively inhibited phospho-ERK with an IC50 values of 63 nmol/L and inhibited cellular viability of BRAF-mutant Malme3M cells with an EC50 values of 0.75 µmol/L. Moreover, there was a strong correlation between activating mutations of the BRAF oncogene and GDC-0879

Pancreatic cancer develops gradually in a series of steps known as pancreatic intraepithelial neoplasia. This is the most prominent stage of cancer. During the early steps, slight changes are seen in a small number of genes. In the later steps, there are abnormalities in several genes and the duct cells become dysfunctional. The most common DNA changes in these conditions affects the KRAS oncogene. KRAS is the mutated gene in PDAC and this gene is said to drive cancer development and progression. This was observed in mouse as human pancreatic tissue is not available for biopsy and animal tissue have the ease of genetic manipulation and cost effective.

In neuroblastomas about 30% of tumours have multiple copies of MYCN, genomic amplification of this proto-oncogene is key in high-risk neuroblastoma contributing towards the aggressiveness, this is usually associated with poor-outcome thus having a malignant phenotype. According to various genome sequencing studies of the neuroblastoma tumour tissue by (reference), a low mutation rate in a small number of individual genes is seen. Recurrent changes in the genes; ATRX, MYCN and anaplastic lymphoma kinase (ALK) were identified to be of biological