Cancer is one of the world’s greatest killer disease with a slow recovery period. A large proportion of the people have been affected by the negating effects of cancer. The quality of life is significantly affected. Cachexia, muscle and weight loss, a weakened immune system among many other health effects have been found to be associated with cancer. However, the advancements in science and technology have led to the development of better ideas, modes, and means to deal with cancer.
One of the effective methods to employ when dealing with the devastating effects of cancer is by interfering with the Notch signaling pathways. The ways and means developed to deal with the negating effects of the Notch signaling system include the use of smart drugs that operate on specific mechanisms of activation and operation of the Notch signaling pathway.
There are over thirty thousand proteins that are useful in the normal conditions of cells i.e. hemostasis. The Notch proteins play such a significant role in managing the normal hemostatic state of cells.
The pathway has aided in the process of proliferation and differentiation of cells (1) (2). The Notch receptors that have been identified are four in number. These receptors are Notch 1, 2, 3 and 4 (4) (3) These four Notch receptors have been found to be similar in appearance. In complete contrast, their extracellular and cytoplasmic domains are different (5). There are two ligands that have been found to be associated with mammals. These ligands have been identified to be delta-like or serrated like in makeup due to similar structural homology. Two serrated like ligands have been identified to be jagged 1 and jagged 2 (6).
The extracellular domains found within the makeup of the Notch proteins have been found to poses a distinct characteristic -they are made up of multiple repeats and also contain the epidermal growth factor that is associated with ligand binding (7). Targeting the Notch proteins with drugs can be most effective in controlling and even eliminating potential malignancies at the end of the day. It is also important to note that there is ligand independent signaling mechanism in the Notch signaling cycle. However the negative regulatory region (NPR) in the Notch system aids in inhibiting both ligand dependent and independent processes (8).
The knowledge collected about the Notch proteins can be very effective when dealing with malignancies and tumors of various kinds. Not only can the Notch proteins and their ligands be inhibited in various types of cancers but also the enzymes within the Notch cycle be stopped hence derailing the onset or progression of a malignant tumor. The prevention of activity of notch, in the development pathogenesis of various kinds of cancer has been seen to be highly significant since it also crosstalks with other important oncogenes in the cancer development process.
In addition, an understanding of the Notch activation system is necessary to treatment modalities associated with cancer. Notch activation is effected when a ligand binds to a surrounding Notch receptor within the environs of cells (9). Once it is activated it leads to the expulsion of the Notch intracellular domain (NICD). This is by means of a systematic process of proteolytic connections by means of metalloprotease, y-secretase and tumor necrosis factor (9).
The second phase of activation can occur on the surface of the cell. It is caused by the connection of a complicated association of proteins which include nicastrin and presenilin among many others.The prevention of y-secretase activity has been found to be very effective in the prevention of the cleavage of receptors of the Notch origin, therefore, the prevention of transduction genes. The Notch genes are maintained in a dormant or inactive state as a result of this inhibition (2) (6) (9).
Genes of the notch origin also play a crucial role in the development of this type of cancer. There are genes that are tissue specific. Other are metastatic and operate on the surface of many organs and tissues. This information significantly shows that Notch has a significant potential in affecting the progression of cancer within body systems.
It is crucial to recognize that the effect of Notch on the body systems has been found to be both beneficial and harmful. Notch can either cause proliferation, survival, differentiation and even apoptosis. On the other hand, Notch may end up causing tumor generation and may end up becoming oncologic or anti-proliferative – paradoxically (1). It has been found that the presence of Notch in human malignancies is usually upregulated rather than downregulated.
The knowledge obtained from the activity of notch is effective in various kinds of tumors and is offering promising results. Pancreatic cancer is the 4th of death in the US (10). In 2009 alone over 35,000 people died as a result of pancreatic cancer in the US. The longevity of life for cancer survivors within the states is below 20% for all stage one patients. And the survival rate for a five year period is below five percent (10).
High prevalence of notch 1 and 2 and its associated ligands and target genes is significant to the progression of cancer (11-16). GSI (which inhibit the activity of y-secretase) aid in avoiding growth and development o cancer. (12). This sign shows the importance of medical knowledge in the activity of the Notch.
Downregulating the activity of notch siRNA or treatment by use of GSI is proportional to a decrease in the proliferation rates caused by pancreatic cancer decreased apoptosis, led to a decrease in migration of cells and a decrease in invasive abilities of pancreatic cancer cells.
However, Notch is up-regulated in a very significant way in the case of Gemcitabine-resistance cancer cells of pancreatic origin, which. It has recently been identified that Notch is involved in the operation of MicroRNA 34 which is responsible for the operation and functioning of pancreatic stem cells and renewal through the direct modulation target notch. This shows that the inhibition of Notch could possibly show a better method for killing the cancer cells and in the process create a better prognosis for the patients who have been affected by pancreatic cancer.
Other than the application of the knowledge attained from Notch in the management of cancer of the pancrease, it is also effective in the treatment modalities in prostate cancer. Cancer of the prostate is one of the most diagnosed and common types of cancer among men. It is the 2nd leading cause of cancer death in the US (10). The overall development and prognosis of prostate cancer involve several numbers of signaling pathways in addition to Notch. This is especially because Notch has also been found to be overly expressed along the lines of prostate cancer cells.
Patients with prostate cancer are found to express the Notch 1 protein in significant proportions. This is especially found in patients with osteoblastic cancer of the prostate Jagged 1 has is expressed in significant proportions in metastatic cancer of the prostate other than localized prostate cancer. For effective management of prostate cancer, it is advisable that the inhibition of Notch 1 and Jagged 1 is crucial is performed.
Downregulating the proportion of Notch and Jagged is effective in preventing metastasis and increasing cell death. Androgen receptor is associated with the Notch. More studies, however, need to be performed to identify the functioning and effectiveness of Notch in the management of cancer of the prostate. However, it is known that using drugs that downregulate the activity of notch and Jagged have proven effective in the management of prostate cancer.
In addition to pancreatic and prostate cancer, breast cancer is another killer disease among a great population of women with cancer. It is the second most common malignancy found among women. There are several treatment modalities that have been used to manage breast cancer. Among this, the treatment modalities that have been used to manage breast cancer are chemotherapy, surgery, and radiation. These modalities work most of the time, however, in some cases they may fail to be effective and tumor recurrence may be experienced. Cumulatively a high level of expression and representation of Notch and its ligand are the causes for poor progress among breast cancer patients. Notch cross talks with other connections in the breast cancer cycle hence derailing further improvements in the overall state of patients. High percentages of Jagged and Notch in patients is also been a cause of poor progression with cancer patients due to the synergistic effect elicited by these two.
Notch has also been identified to be responsible for the regulation of slug, estrogen receptor, Slug, and many other crucial signaling proteins in breast cancer management. By preventing the activity of Notch breast cancer is controlled more effectively. Targeting the Notch signaling is appropriate method of controlling cancer of the breast.
In combination with the other types of cancers already discussed, lung cancer is also a member of this killer cancerous diseases. It is able to kill more than three thousand people day by day. The progression of lung cancer and worsening prognosis of patients is related to notch. Notch 1 and Notch 2 are contained in high levels this type of cancer (10).Oxygen levels have been found to affect the expression of Notch because the expression of Oxygen is useful in the controlling of hypoxia and cancer of hypoxic in nature (10)
Conclusion
In conclusion, the importance of inhibition of Notch as a treatment modality cannot be over-emphasized. Not only is the inhibition of the ligands, enzymes, and molecules involved in the notch signaling effectively in the treatment process of cancer but also in the termination of stem cells associated with cancer. The context of notch termination is also essential. Notch sometimes plays a very positive function in the activity of cells. Drug modalities working on specific target types of Notch and in specific locations are effective in improving patient’s prognosis
Reference list.
Essay Writing Service Features
Our Experience
No matter how complex your assignment is, we can find the right professional for your specific task. Contact Essay is an essay writing company that hires only the smartest minds to help you with your projects. Our expertise allows us to provide students with high-quality academic writing, editing & proofreading services.
Free Features
Free revision policy
$10Free bibliography & reference
$8Free title page
$8Free formatting
$8How Our Essay Writing Service Works
First, you will need to complete an order form. It's not difficult but, in case there is anything you find not to be clear, you may always call us so that we can guide you through it. On the order form, you will need to include some basic information concerning your order: subject, topic, number of pages, etc. We also encourage our clients to upload any relevant information or sources that will help.
Complete the order form
Once we have all the information and instructions that we need, we select the most suitable writer for your assignment. While everything seems to be clear, the writer, who has complete knowledge of the subject, may need clarification from you. It is at that point that you would receive a call or email from us.
Writer’s assignment
As soon as the writer has finished, it will be delivered both to the website and to your email address so that you will not miss it. If your deadline is close at hand, we will place a call to you to make sure that you receive the paper on time.
Completing the order and download