(6 Points) Describe three aberrations to this pathway that could potentially lea
ID: 93089 • Letter: #
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(6 Points) Describe three aberrations to this pathway that could potentially lead to tumor formation. What is the consequence to the remainder of the pathway and cellular response with each aberration?
(6 Points) For one of the aberrations you listed above (let me know which you are selecting), determine a molecular target for a new cancer therapy that could correct the issue. We will assume that you are directly designing the “drug” for this therapy, so would you design an inhibitor or an activator for your molecular target? How will this help?
(8 Points) As a researcher, your job may be done at this point (after you contact a pharmaceutical company with your findings), but there are still four steps remaining in the normal process of development of new cancer therapies. Give a brief explanation of what will occur in each of the remaining steps until your drug is made available to the masses.
Use the following information to answer questions #12-14. Ligand M BC493 LH MBc493. Receptor 2 8 ACT 9b REP 9b ACT 9b Activates REP DNase Apoptosis Cell Proliferation 9a ACT DNA Repair Cell Membrane Nuclear MembraneExplanation / Answer
There possibly three aberrations which could possibly be implemented in the cell and will lead to tumor formation:-
1) Conformational change in the ligand MBC493, which will stop the whole pathway.
2) Mutation in the lysine residues of the protein 5, which could possibly inhibit ubiquitination.
3) Increase in the amount of the protein which prevents the binding of 9b REP.
All the above aberrations will ultimately leads to the tumor formation. The consequence of these aberrations is tumor formation.
The most likely cellular response after tumor fromation would be immunosurveillance and immunoediting.
In immunosurveillance the lymphocytes act as sentinels in recognizing and eliminating continuously arising, nascent transformed cells. Immunosurveillance appears to be an important host protection process that decreases cancer rates through inhibition of carcinogenesis and maintaining of regular cellular homeostasis.
Immunoediting induces selection for certain tumour cells, which loose dominant tumour-specific antigens allowing for tumour progression. It has three main phases: elimination, equilibrium and escape.
Molecular target for the protein that prevents the binding of 9b REP and can be used aas a cancer therapy:-
However, extracellular proteins and some cell surface proteins are taken up by endocytosis and degraded within lysosomes. These organelles contain several acid-optimal proteases, including cathepsins B, H, and D, and many other acid hydrolases. Some cytosolic proteins are degraded in lysosomes after being engulfed in autophagic vacuoles that fuse with lysosomes . In most cells, this process is accelerated by the lack of insulin or essential amino acids and in liver by glucagon . There are other cytosolic proteolytic systems in mammalian cells. The Ca2+-activated (ATP-independent) proteolytic process involves the cysteine proteases termed calpains. These proteases seem to be activated when cells are injured and cytosolic Ca2+ rises, so they may play an important role in tissue injury, necrosis, and autolysis . Another important family of cytosolic proteases is the caspases that cleave proteins after aspartic acid residues. These enzymes, which are cysteine proteases, are critical in destruction of cell constituents during apoptosis.
The above mentioned are the several types of protein degradation, which could be possible by firstly identifying our protein and the 3D structure of the protein.
After identification, there could be several drugs:-
Before the drug reaches to the masses, their are several clinical trials, which are required for the drug testing process:-
Phase I studies assess the safety of a drug or device. This initial phase of testing, which can take several months to complete, usually includes a small number of healthy volunteers (20 to 100), who are generally paid for participating in the study. The study is designed to determine the effects of the drug or device on humans including how it is absorbed, metabolized, and excreted. This phase also investigates the side effects that occur as dosage levels are increased. About 70% of experimental drugs pass this phase of testing.
Phase II studies test the efficacy of a drug or device. This second phase of testing can last from several months to two years, and involves up to several hundred patients. Most phase II studies are randomized trials where one group of patients receives the experimental drug, while a second "control" group receives a standard treatment or placebo. Often these studies are "blinded" which means that neither the patients nor the researchers know who has received the experimental drug. This allows investigators to provide the pharmaceutical company and the FDA with comparative information about the relative safety and effectiveness of the new drug. About one-third of experimental drugs successfully complete both Phase I and Phase II studies.
Phase III studies involve randomized and blind testing in several hundred to several thousand patients. This large-scale testing, which can last several years, provides the pharmaceutical company and the FDA with a more thorough understanding of the effectiveness of the drug or device, the benefits and the range of possible adverse reactions. 70% to 90% of drugs that enter Phase III studies successfully complete this phase of testing. Once Phase III is complete, a pharmaceutical company can request FDA approval for marketing the drug.
Phase IV studies, often called Post Marketing Surveillance Trials, are conducted after a drug or device has been approved for consumer sale. Pharmaceutical companies have several objectives at this stage: (1) to compare a drug with other drugs already in the market; (2) to monitor a drug's long-term effectiveness and impact on a patient's quality of life; and (3) to determine the cost-effectiveness of a drug therapy relative to other traditional and new therapies. Phase IV studies can result in a drug or device being taken off the market or restrictions of use could be placed on the product depending on the findings in the study.
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