Anticancer Drugs and Chemotherapy

Abstract

In the past 50 years cancer treatments have increased the amount of successfully treated cancer patients. Before the 1990s surgery or chemotherapy were the only options. Recently, scientist have discovered qualities of cancer and formed new anti-cancer drugs less harmful to the whole body. These anti-cancer drugs paired with chemotherapy are the current approach to the majority of cancer patients. Each type of cancer behaves differently and consequently must will be treated in a diverse way. The main goal in the twenty first century is to perfect drugs that select only cells containing cancer and cause apoptosis and make prevention a larger focus [14].

It is known how to cause programmed cell death; the difficulty lies in the drug determining the proper cells [14]. If screening for cancer takes place in early stages, the patients have much higher success rates. Creating a screening process that uses the found characteristics of cancer to locate it at early stages is another current issues [15].

Introduction

Cancer is caused by the rapid abnormal growth of cells, as the cells gather, they form a mass, called a tumor. Cancerous tumors are labeled “malignant” meaning they spread and invade other areas of the body. Unfortunately, cancer can develop anywhere in the human body [10]. Cancer can develop depending on environmental factors such as exposure to tobacco, radiation, and chemicals or it can be on a cellular level such as genetics, hormones, personal health, and existing conditions. The theory for which cancer develops is the transformation of normal cells into cancerous takes place in a change in the replication process on a molecular, biochemical, or cellular level [17].

There are infinite possibilities for any of these changes to take place during proliferation, differentiation, and before cell death [17]. Different types of cancer are treated in different ways; the most common being chemotherapy and additional anticancer drugs if surgery isn’t an option or immunotherapy and hormone therapy. Chemotherapy was initially used in the 1940s and with the knowledge of modern biology and chemistry have made significant strides in curing different types of cancer. Oncology has become the largest therapeutic area in the pharmaceutical industry in terms of the number of projects, clinical trials and research and development spending [1].

The new age of anticancer drugs arose abundantly in the 1990s. Their approach is targeted therapy, which attempted to abstain from killing healthy cells in the treatment process. Immunotherapy, termed biologic therapy, increases the immune system to better the body to fight cancer. It utilizes substances naturally made in the body to improve the function of the immune system [18]. Immunotherapy aids in teaching the body to differentiate which cells are cancerous. Lastly, hormonal therapy uses hormones to slow the progression of cancer. It is mostly used to treat breast and prostate cancer [19]. Scientist and pharmacist face challenges in detecting cancer sooner and finding only cancerous cells to kill. The aim of this paper is to discuss the role of biochemistry in the evolution of chemotherapy and anticancer drugs, and the challenges scientist and pharmacist must overcome to cure cancer.

Chemotherapy

During World War II, exposure to highly toxic mustard gas created changes in blood composition. Research to make the most efficient chemical weapons continued, but also led to the exploration of protection to exposure. During their studies, nitrogen mustard was found to reduce cancer of the lymph nodes. Nitrogen mustard created a model for future, more effective drugs, to stop the growth of cancer cells [4].

Chemotherapy became prevalent in the 1940s, beginning the with Sidney Farber. Farber was a pediatric pathologist who discovered aminopterin, a part of folic acid which aided in the prevention of DNA replication [4]. In 1948, he performed a study that found aminopterin led to remission for children with leukemia [5]. His findings led researchers to focus on the prevention of cell growth to treat cancer. This created the first large wave of cancer research. These discoveries led to the modern chemotherapy treatment drug, methotrexate. Methotrexate cured the firsts case of metastatic cancer in 1956 [4].

Chemotherapy differs from surgery and radiation because it doesn’t target a specific region, instead it spreads throughout the body making it the best option for metastasized cancer. It is used to either shrink a tumor or stop the growth/spread of tumors [6]. Chemotherapy is used in several different methods for varying reasons. It may be suggested to use before surgery to help reduce the size of the tumor. This method is referred to as neoadjuvant therapy. It may also be used after surgery to kill any remaining cancerous cells, this is called adjuvant therapy [6]. Chemotherapy may be used alone or paired with other treatment plans depending on the aggression of the type of cancer. It’s beneficial to patients experiencing pain caused by their tumor because it’s ability to shrink the physical size. Chemotherapy is recommended to almost all patients, it may not be necessary is the cancer is detected in early stages and is eradicated through surgery.

Humans are made up of 100 trillion cells. Cancer cells grow out of control during cellular replication. Chemotherapy drugs can attack resting cells or cells in the replication process, there is no way to treat the healthy and cancerous cells differently. The drugs bind to DNA to prevent cell division. Chemotherapy drugs also attack normal cells that are duplicating [9]. Chemotherapy can be administered in many ways; infusions, pills, shots, creams, insertion, and targeted. Infusion is the most common method; the specific chemo drug is given through the veins [9]. Creams are used mainly for skin cancer patients [7].

There are different types of chemical therapy drugs. Oncologist create specific treatment plans depending on the patient’s type and stage of cancer, age, medical history, and reoccurrence. The oldest chemotherapy drug damage the DNA, they’re called alkylating agents. The kills the bad and good cells, so are recommended at lower dosages to lessen the effects [8]. Antimetabolites interfere with the normal metabolism of cells, stopping their ability to grow. Anthracycline and topoisomerase chemotherapy attacks from within the cancer cell, specifically the enzyme that helps DNA divide. High doses on anthracycline can damage the lungs or heat, therefore a recommended for a short period of time. Mitotic inhibitors stop your body from producing the proteins that cancer cells need to grow, preventing the cancer cells from making more copies of themselves [8].

Each patient’s treatment plan utilizing chemotherapy is different. Their type, dosage, frequency, and administration of chemotherapy depends on many factors. If chemotherapy isn’t the optimal treatment plan for a patient, it typically is pair with other anti-cancer drugs methods discussed below.

Since chemotherapy destroys cells, it can damage the cells that make up hair follicles, digestive tract, reproductive system, mouth, and cells found in bone marrow [20]. Therefore, chemotherapy recipients experience different symptoms depending on length and strength of treatment. The side effects chemotherapy causes in patients are fatigue, hair loss, easier bruising, anemia, higher risk of infection, nausea, loss of appetite, digestion issues, soreness of mouth and tongue, tingling due to nerve problems, dryness of skin, urine changes, mood changes, and fertility problems [20]. There are supportive drugs available to manage or relieve side effects from cancer or cancer treatments. Doctors will also discuss diet and vitamins that can relieve the effects of chemotherapy [20].

Anti-Cancer Drugs

Before 1990 all cancer drugs revolved around killing cells to prevent the rapid replication of DNA. The new age of cancer drugs focusses on targeted therapies versus previously chemotherapy. Targeted therapy utilizes drugs to target specific gene sequences or proteins causing the abnormalities, while not harming healthy cells [11]. The three main types of targeted therapies are growth signal inhibitors, angiogenesis inhibitors, and apoptosis-inducing drugs.

Growth signal inhibitors have the abilities to guide cells to grow and divide [11]. The body creates antibodies once a foreign species, antigen, is identified. The antibodies detect the antigen to indicate something is wrong in order to trigger the immune system. Recently, scientist have analyzed the antigen in cancers and developed antibodies that can target only the cancerous cells. “This technology allows treatment to target specific cells, causing less toxicity to healthy cells” [12].

The next targeted therapy is angiogenesis inhibitors. Angiogenesis is the creation of new blood vessels [11]. New blood vessels heal the body by increasing circulation of blood through the body. The angiogenesis process creates new blood vessels that would give a tumor its own blood supply and allow it to grow [11]. In the 1970 Judah Foldman believed there was a way to constrain a tumors blood supply. Thus, angiogenesis inhibitors were created to stop tumors from making the new blood vessels necessary to grow [11].

The last targeted therapy is apoptosis-inducing drugs. Apoptosis is programmed cell death. The aim of many cancer treatments is to damage a cell’s DNA, naturally leading to apoptosis. The goal for targeted treatment is to induce apoptosis in only the cancer cells, making the process unnatural. Difficulties arise with this treatment due to finding specific cancerous cell features and inducing only those with programmed death [14].

Each method faces differing challenges. With each cancer differing in size, aggression, and growth rate there is not a “cure-all” solution. For examples, a gene called KRAS controls the growth of the tumor [16]. About 40% of colorectal cancers have this gene mutation. When it is prevalent, the usual colorectal targeted therapies are not effective [16].

Future work

The next steps towards curing cancer lie in prevention and treatment. In order to find cancer in the early stages, screening needs to take place more frequently along with more sensitive detection of cancerous cells. If a biologist can distinguish the characteristics of different cancer cells from normal cells that can be detected in a CT scan or blood work, cancer can be found before its more difficult to treat [15].

The advances in treatment are more complex. It is still crucial to find properties which distinguish the normal cell from the cancer cells. “One such property is the genetic instability that results from loss of chromosome maintenance or DNA repair mechanisms” [15]. Once this is done treatments similar to targeted therapies can be developed. Whether it's from finding specific DNA sequences or proteins prevalent in cancer cells, there must be a way to kill only cancers cells, not healthy cells. The anti-cancer drug approaches need to modify to more specifically target a quality within a cancer cell. This specificity will be a larger challenge from biologist and chemist. As scientist better understand the process of tumor progression, treatment methods can be more fine-tuned, and hopefully, lead to curing cancer [15]. Other difficulties come with the rapid growth of cancer and its ability to mutate. As cancer mutates it can build resistance to previous treatments [15].

References

1. Xu, J., & Mao, W. (n.d.). Overview of Research and Development for Anticancer Drugs. Retrieved from https://file.scirp.org/pdf/JCT_2016102114074275.pdf
2. Stringer, J. L., & Snyder, I. S. (2018, November 15). Anticancer Drugs. Retrieved from https://www.britannica.com/science/anticancer-drug
3. Ali, & U, A. (2018, November 02). Nanoemulsion as a Vehicle in Transdermal Drug Delivery. Retrieved from http://biomedicine.imedpub.com/nanoemulsion-as-a-vehicle-in-transdermal-drug-delivery.php?aid=23884
4. Evolution of Cancer Treatments: Surgery. (n.d.). Retrieved from https://www.cancer.org/cancer/cancer-basics/history-of-cancer/cancer-treatment-surgery.html
5. Miller, D. R. (2006, July). A tribute to Sidney Farber-- the father of modern chemotherapy. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/16803563
6. How Is Chemotherapy Used to Treat Cancer? (n.d.). Retrieved from https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/chemotherapy/how-is-chemotherapy-used-to-treat-cancer.html
7. Chemotherapy. (2017, April 27). Retrieved from https://www.mayoclinic.org/tests-procedures/chemotherapy/about/pac-20385033
8. Chemotherapy: How the Drugs That Treat Cancer Work. (n.d.). Retrieved from https://www.webmd.com/cancer/how-chemo-works
9. C. (2012, January 23). How Cells Divide and How Chemotherapy Works. Retrieved from https://www.youtube.com/watch?v=VRhz3DhjG5M
10. National Cancer Institute. (n.d.). Retrieved from https://cancer.gov/search/results
11. A. (n.d.). Evolution of Cancer Treatments: Targeted Therapy. Retrieved from https://www.cancer.org/cancer/cancer-basics/history-of-cancer/cancer-treatment-targeted-therapy.html
12. Cleveland Clinic Cancer. (n.d.). Trastuzumab. Retrieved from http://chemocare.com/chemotherapy/drug-info/Trastuzumab.aspx
13. Masters, J. R. (1990, December). Biochemical basis of resistance to chemotherapy. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/2284441
14. Hickman, J. A. (1992, September). Apoptosis induced by anticancer drugs. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/1327566
15. Alberts, B. (1970, January 01). Cancer Treatment: Present and Future. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK26811/
16. Understanding Targeted Therapy. (2019, February 28). Retrieved from https://www.cancer.net/navigating-cancer-care/how-cancer-treated/personalized-and-targeted-therapies/understanding-targeted-therapy
17. Hejmadi, M. (n.d.). Introduction to Cancer Biology - University of Georgia. Retrieved from http://csbl.bmb.uga.edu/mirrors/JLU/DragonStar2017/download/introduction-to-cancer-biology.pdf
18. Understanding Immunotherapy. (2019, January 29). Retrieved from https://www.cancer.net/navigating-cancer-care/how-cancer-treated/immunotherapy-and-vaccines/understanding-immunotherapy
19. Hormone Therapy for Breast Cancer. (n.d.). Retrieved from https://www.cancer.gov/types/breast/breast-hormone-therapy-fact-sheet
20. Chemotherapy Side Effects. (n.d.). Retrieved from https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/chemotherapy/chemotherapy-side-effects.html

Did you like this example?

1194

50