Summary of research plan
Development of drugs with high potency and inhibitory activity against specific activating mutation, while showing significantly less activity against wild type mutations, made testing specific sensitizing mutation necessary. (1) (EGFR) T790M mutation a successful example of a biomarker for non-small cell lung cancer (NSCLC) treatment with Osimertinib that gained a wide acceptance in clinical practice in Europe and US (), One question that needs to be asked, however, is whether testing for similar mutations in different cancer will be of clinical value. an unknown subpopulation of patients with CRC will have an activating EGFR mutation, such as L858R, which is thought to activate the receptor constitutively, regardless of ligand status promoting cellular proliferation and growth. in patients with colorectal cancer, Targeting activated EGFR, hypothetically, will lead to growth inhibition of cancer cell dependent on the oncogenic drive of sensitising EGFR mutation. This project aims to investigate the role of EGFR (L858R/+/+) as a biomarker for AZD 9291 (Osimertinib) treatment, using SW48 cell line with a wild type mutation of EGFR and Heterozygous knockin of EGFR activating mutation (L858R/+/+), to investigate the mechanism of resistances if cells developed resistance and to test the overlap between Osimertinib and AZD5363, palbocidib and selumetinib.
This work should improve treatment outcome for patients with CRC with EGFR sensitising mutation
Significance: understanding the mechanism of drug resistance in cancer leads to developing more potent drugs.
Optimal management of NSCLC now requires that tumours be screened for a certain range of predictive and prognostic biomarkers that help to predict sensitivity to targeted therapy and estimate prognosis respectively . For NSCLC, much of the work in the past years has been focussed on mutations of the epidermal growth factor receptor (EGFR) and on the abnormal fusion of the anaplastic lymphoma kinase (ALK) being inhibited successfully with EGFR tyrosine kinase inhibitors (TKI) and crizotinib respectively. Targeted agents are now being rationally designed to inhibit particular mutations leading to a more streamlined clinical trial process. In this review, we will examine the major subtypes of driver mutations that have been identified in NSCLC and relevant targeted therapies available both now, and in the foreseeable future.
We would like to own a product series covering our customers suffered from all illness segmentation of the OTC cold and allergy remedy market. We have totally launched 3 products, which played different roles in our product portfolio and have different attribute association.
Choosing one aspect of paper and focusing on all products and competitors so the material is available when the time comes to write the paper
The epidermal growth factor receptor (EGFR) is the cell-surface receptor for extracellular protein ligands. EGFR family has four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/c-neu, Her 3 and Her 4. Mutations affecting EGFR expression or activity could lead to cancer.
Nature gave us this ability, let us adapt to different environments, but cancer is not only retains the basic evolutionary capacity, and stronger, we gave it a drug against cancer cells are constantly changing, trying to escape the effects of the drug. According to” Ceritinib in ALK-Rearranged Non-Small-Cell Lung Cancer", by New England Journal of Medicine, Ceritinib in clinical trials of time, they found a lot of cancer a few months after treatment discarded ALK gene mutation , and produce new mutations to help cancer grow so fast speed of evolution, nature always makes me sigh in front of human
Drug development is the process of bringing a new pharmaceutical drug to the market. The main goal of drug development is to produce safe and efficacious therapeutic products for the promotion of health, and the prevention, cure and treatment of disease.
London Drugs (LD) is currently in the process of implementing a customer loyalty program called LDExtras .While the
The other influential components such as PI3K, ERK, and Ras have been previously explored in multiple cancer types. However, the influential components consist of the most important drug candidates that block cell proliferation in cancer cells. Some of these components have been associated with the drug resistance. For example, in non-small cell lung cancer, EGFR showed mutation in its kinase domain, Epithelial–mesenchymal transition, and mechanisms to develop resistance to gefitinib [35]. In colorectal, and head and neck cancers KRAS mutation, EGFR-S492R mutation, and increased ErBb signaling are responsible for resistance
Recently, multitherapy are used as it is inexpensive and to avoid causing resistance. [7]. Receptor tyrosine kinases play a great role in signal transduction pathways that regulate cell division. One of the most important growth factor receptor kinases that have been identified is epidermal growth factor receptor (EGFR) [8, 9]. Its role in breast cancer, [10] lung cancer [11-13] and in hormone-refractory prostate cancer [14] has been studied. EGFR PTK inhibitors were used in the treatment of malignant epithelial diseases. In cancer clinical trials EGFR kinase inhibitors were evaluated [15-29]. Some quinazoline derivatives show potent inhibition of epidermal growth factor receptor [15-25]. Some tyrosine kinase inhibitors (TKIs) were approved by FDA for cancer treatment
An amplification of this gene has been reported in numerous cancers, including breast and ovarian tumors. In this case, the patient was shown to be C-erbB2 positive (HER2/neu) IBC was diagnosed in the left breast, two years after the patient’s right breast mastectomy. Furthermore, ERBB2 or HER2 protein overexpression or gene amplification is a predictive marker for response to trastuzumab (Herceptin) in patients with breast cancer. This type of protein can be confirmed through the immunohistochemistry test. If the patient has a score 3+ on the test, the patient may be considered eligible for treatment with trastuzumab. On the other hand, a patient who does not have gene amplification of score 0 or 1+ may be considered for a targeted
Pharmaceutical Sciences is a topic that has interested me for a while now. What I can say about this topic is that it will help humanity grow as a whole and keep everyone moving forward. This is a topic where people really need to think about what goes behind the scenes of your average pharmacies. Once people start to think about it, they would start to realize that the science that happens is extremely crucial to mankind as we know it. Without this kind of science, where would humans be today? Would we have the ability to evolve the way we have? How far would humans make it to creating today’s future as we know it? The simple answer to all these questions is
Contract research organizations run hundreds of clinical trials per year to evaluate new drugs for safety and efficacy. The phase 1 of these trials consists of testing the safety of a drug; therefore, it does not require the individual being tested to have the disease the drug is aiming to cure. However, it is important that an individual takes part of a single trial at one particular moment in time and that he refrains from participating in another trial prior to a washout period determined by his current trial participation. Unfortunately, people do not always follow the rules. In phase 1 trials, some people are lured by the monetary compensation offered in return for their participation. These people attempt to participate in more than
Drug research is connected to a range of academic studies such as biology, pharmacology, medicinal chemistry and toxicology. Pharmaceutical researchers can design novel therapeutic drugs based on these studies above. The invention of new drug can be divided by function into two stages: drug discovery and drug development. Drug discovery is the process by which a new drug candidate is found and identified. Distinctively, bringing a new drug candidate to the market through clinical trials is called drug development. The first part of this essay provides an overview of drug discovery and pre-clinical research and development
There are many different methods of dispersing and accumulating data from subject self-reports, but for the purpose of this research proposal we have elected to adopt a method used in relatively recent study published by the Journal of Drug Issues entitled: “Substance Use, Drug Treatment, and Crime: An Examination of Intra-Individual Variation in a Drug Court Population”.