Cancer is the most dangerous enemy of human health, and in terms of mortality in the world, it ranks second only to cardiovascular diseases. Still, regarding the fear that people have, it is precisely the first. Many thousands of researchers seek to understand its causes, find ways to prevent it, determine predisposition, and improve its treatment. The treatment of malignant tumors is a complex task, as each case requires a different approach and its own medicine. The purpose of this research paper is to discuss the current drug Keytruda and how it works at the biochemical and cellular level.
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In order to fight the tumor, it is necessary to understand the reasons for its development. Cancer is a malignant tumor in which cells reproduce uncontrolled, with the invasion of the tissue and metastasis to distant organs with lymphatic or blood flow. Almost any oncological disease is based on the violation of the processes of regulation of tissue growth. Cells in our body are regularly updated, and in the process of their division, there is always the possibility of a mutation. This also happens in natural conditions, but the frequency of occurrence increases significantly when exposed to adverse factors such as carcinogens or ionizing radiation.
It is worth noting the relevance of finding alternative medicines. The problem of cancer remains a priority for modern society. The control figures for cancer incidence are striking. According to statistics provided by Siegel, Miller, and Jemal (2019), more than six hundred thousand cancer deaths are expected this year, which is more than 1,700 American deaths per day. In addition, a particular type of cancer, melanoma, is increasingly spreading among young people.
The annual increase in melanoma cases among children under 19 years of age was 2 percent between 1970 and 2009 (Raedler, 2015). For this reason, almost every scientific laboratory that aims to combat cancer is committed to releasing its drug. Furthermore, it is not possible to list all the drugs currently used to treat disease: dozens of different medications can be used to treat a tumor, for example, in the stomach. In most cases, the antitumor drug is available either in ampoules as a ready-made oral solution or in infusion solution bottles.
Classic drugs that suppress or destroy tumor growth showed their effectiveness exactly until the other side of the use of radical drugs was revealed. For example, humanity has a long known antitumor agent from the group of anthracycline antibiotics Doxorubicin, the mechanism of action of which is to bind DNA and suppress the synthesis of nucleic acids. However, Doxorubicin has cumulative toxicity: it manifests itself in myocardial damage with reduced contractility and clinical symptoms of chronic heart failure.
The innovative tool Keytruda was specially designed to influence the tumor with the help of mechanisms of own immune response, without causing a negative effect on the overall health of the patient. Keytruda is considered an innovative treatment for melanoma with metastasis (Raedler, 2015). Melanoma is not the most common type of cancer, but it is known to be almost inoperable (Siegel et al., 2019). Unlike other treatments, it has a number of significant advantages. First, Keytruda acts selectively without damaging or dying healthy tissue cells. Secondly, unlike its analogs, Keytruda can treat inoperable melanoma, head and neck tumors, and stomach cancer.
Pembrolizumab, the main active ingredient of the original Keytruda, was first approved in 2015 by the European Commission for the treatment of melanoma. A number of States then recommended the use of the drug, increasing the availability of the drug. It was obtained by recombinant DNA research in Chinese hamster ovarian cells. In addition to the active ingredient pembrolizumab, the preparation also includes auxiliary substances L-histidine, L-histidine hydrochloride monohydrate, sucrose, water for injection, and polysorbate. Keytruda is a clear or yellow liquid for infusion.
Keytruda is both an immune and antitumor drug. Own immunity of the oncological patient reacts to the growth of a malignant tumor, most often inactive, recognizing it as an integral part of the body. In response to the tumor, immune cells synthesize a very similar protein antibody to pembrolizumab, but not enough to destroy the malignant concentration process. The biochemical mechanism of action consists in blocking the interaction between tumor cell receptors and the corresponding ligands. Some cancer cells have PD-1 receptors located on them, which are combined with the antibody to trigger reactions that lead to cell death. PD-1 is a receptor that is an immune reference point that limits the activity of T-lymphocytes in peripheral tissues. Tumor cells can use the PD-1 signaling pathway to inhibit active T-cell immunological surveillance.
Pembrolizumab, in turn, is a high-affinity antibody that binds specifically to the PD-1 receptor and is inhibited by a double blockade of the PD-1 signaling pathway, including PD-L1 and PD-L2 ligands on tumor or antigen-presenting cells (Ott et al., 2019). In terms of biochemical structure, pembrolizumab is an antibody of type IgG4 with a molecular weight of about 149 kDa. By inhibiting the receptor’s bond with its ligands, pembrolizumab reactivates cytotoxic T-lymphocytes in the tumor’s microenvironment and thus revives antitumor immunity (Raedler, 2015). Keytruda’s monoclonal antibody is an active cancer wrestler that is synthesized in a laboratory tube and enters the patient’s body in a ready-made form and sufficient concentration.
The use of Keytruda is most often associated with the development of immune-mediated adverse reactions. Pneumonia is one of the most common side effects, but only 9% of participants in clinical trials of Keytruda were stopped (Raedler, 2015). In addition, pembrolizumab can cause harm to pregnant women when taking the drug, and there is a medical recommendation for them to choose a minimum dose of the substance.
The efficacy and safety of Keytruda have been studied in numerous studies on the treatment of common melanoma, stomach cancer, and other tumors. At thematic conferences and symposiums, doctors share good practices in the treatment of common melanoma, stomach cancer, and different types of tumors. The same is true of the studies – the results are promising and optimistic (Ott et al., 2019). The leading indicators are survival rate without progression, overall survival rate, overall response rate, and response time.
One of the main challenges for humanity in the fight against cancer. Despite the diversity of existing anticancer drugs, most of them cause irreparable harm to the patient’s health as a result of non-local effects. Keytruda, launched in 2015, is an innovative drug based on a natural antibody called pembrolizumab that selectively blocks tumor receptor binding to ligands. Keytruda has been shown to be effective in controlling the tumor, and patients tolerate side effects caused by the drug without significant complications.
Ott, P. A., Bang, Y. J., Piha-Paul, S. A., Razak, A. R. A., Bennouna, J., Soria, J. C.,… Lopez, J. (2019). T-cell–inflamed gene-expression profile, programmed death ligand 1 expression, and tumor mutational burden predict efficacy in patients treated with pembrolizumab across 20 cancers: KEYNOTE-028. Journal of Clinical Oncology, 37(4), 318-327.
Raedler, L. A. (2015). Keytruda (pembrolizumab): First PD-1 inhibitor approved for previously treated unresectable or metastatic melanoma. American Health & Drug Benefits, 8(Spec Feature), 96-100.
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Siegel, R. L., Miller, K. D., & Jemal, A. (2019). Cancer statistics, 2019. CA: A Cancer Journal for Clinicians, 69(1), 7-34.