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The Future of Cancer Research

About four out of 10 Americans will have cancer at some point in their lifetime, and with unhealthy modern lifestyles and diets, the rates of many types of cancers are rising. According to CA: A Cancer Journal for Clinicians, cases of breast, uterine, and prostate cancer have been “of concern” and rising in the United States. Despite two decades of decline, the prostate cancer incidence rate rose 3% per year from 2014 through 2019. Unfortunately, there is no single definitive cure for cancer, and there most likely never will be. However, improvements in screening and treatment have resulted in steadily improved cancer death rates since the early 1990s. Nevertheless, various innovative treatments continue to be developed to tackle the disease.


Cancer can’t be cured – at the very least, the chance there is an all-encompassing cure to cancer is as likely as an all-encompassing cure to all infectious diseases. Cancer isn’t one disease. It’s a broad category of diseases. There are even differences and different challenges between types of cancers. For example, there are over 120 different types of brain cancer. Glioblastomas and ependymomas have vastly different treatments and prognoses. Even the same kind of cancer can manifest differently in different people. The term tumor heterogeneity describes how different tumor cells can show varying traits, including shape, size, metabolism, gene expression, proliferation, and metastatic potential. As cancer progresses, it generally becomes more heterogeneous, resulting in cells with different levels of sensitivity to treatment. Heterogeneity tends to result in more resistant cancers that are difficult to treat. Another possible result of cancer progression is metastasis. Metastasis is the development of malignant cancers away from the original site of the tumor. Having to target cells in various locations makes treatment a more challenging endeavor. In addition, cancer isn’t a foreign invader trying to attack the body- cancer cells are human cells that have gone awry. Many of the treatments that hurt cancer also hurt the surrounding healthy cells.


Primary treatment is treatment intended to remove the cancer or kill all of the cancer cells. The most common primary treatment for cancer is surgery. However, surgery isn’t feasible for many cancers. Leukemia (blood cancer) and lymphoma (lymphatic system cancer) are often systemic and can’t easily be removed from one location. For similar reasons, surgery often isn’t feasible for cancer that has metastasized. Surgery is also impractical in cases where cancer is located in areas that are difficult to reach or when cancer is located near delicate tissues, making surgery risky due to the possibility of harming surrounding areas. Although extremely rare, it is possible for surgery to cause cancer to spread. Chemotherapy and radiation therapy are also commonly used for primary treatment, but they are used for adjuvant treatment (treatment to kill any cells left after primary treatment) as well. Even with these 21st-century cancer treatments, cancer can regrow in a process called recurrence or relapse. Luckily, several new techniques are being developed with targeting drug resistance in mind.


Many new cancer treatments involve modifying the body’s natural defense mechanisms to better target cancer. Monoclonal antibodies (mAbs) are laboratory-produced antibodies (proteins that respond to specific antigens, toxic or foreign substances) designed to target the proteins on specific cells, such as cancer cells. A specific monoclonal antibody may be designed to flag cancer cells, block cell growth, directly attack the cancer cell, deliver chemotherapy, or perform other functions. There are several types of mAbs, the most common type being naked mAbs.



Monoclonal antibodies

Naked mAbs are antibodies with no drug or radioactive substance attached. Most naked mAbs attach to antigens on cancer cells, but some work by binding to antigens on other non-cancerous cells. They tend to work by either strengthening the immune response or by attaching to and blocking antigens on cancer cells that help them spread. On the other hand, conjugated mAbs are combined with a chemotherapy drug or radioactive substance. Radiolabeled antibodies have small radioactive particles attached to them. In contrast, antibody-drug conjugates (chemolabeled antibodies) have chemotherapy (or other) drugs attached to them. Both of these mAbs take these substances directly to the cancer cells. The mAb circulates throughout the body until it can find the target antigen, delivering the toxic substance where it is needed most. This lessens the damage to normal cells in other parts of the body. There are also bispecific monoclonal antibodies; these drugs are made up of parts of 2 different mAbs, meaning they can attach to 2 different proteins simultaneously.

Unfortunately, monoclonal antibodies aren’t a perfect solution. Although their side effects tend to be less severe than chemotherapy’s, monoclonal antibodies often have allergic-reaction-like side effects because mAbs are proteins. Monoclonal antibodies can also be expensive- the average annual cost is around $100,000. Scientists continue to develop treatments using the immune system to attack cancer cells, so it begs the question: Why doesn’t the immune system ever successfully fight off the cancer?


Cancer cells can find ways to evade the immune system. One way they do so is by presenting proteins on their surfaces that target immune checkpoints. This dampens the ability of immune cells to kill them. A type of cancer therapy called immune checkpoint inhibition blocks these interactions. Cancer not only avoids detection by the immune system but also affects how the immune system works against other illnesses- cancer can limit the nutrients available to immune cells. Cancer has high metabolic activity, and the disorganized vasculature in the microenvironment creates competition between cancer and immune cells for nutrients. This weakens the immune system and makes someone with cancer more vulnerable to other illnesses.


Along with modifying the body’s natural defenses, scientists are finding new ways to alter the body’s genetic code to prevent and treat cancer. A gene can’t easily be inserted directly. It usually has to be delivered using a carrier called a vector. Gene therapy is a treatment that involves replacing a faulty gene or adding a new gene in an attempt to cure disease. Gene therapy has the potential to treat a wide range of diseases, such as cystic fibrosis, heart disease, diabetes, hemophilia, AIDS, and cancer. Despite how promising gene therapy is, there are several issues. Firstly, using a virus to deliver the therapy comes with risks. The presence of the virus could trigger an immune response or the virus to cause infection. There is also a risk that genes are delivered to the wrong cells or spots in the DNA. This could damage healthy cells or cause cancer. Critics of gene therapy also have ethical concerns, fearing that normalizing the alteration of genes could lead to discrimination against those with disabilities or that humans shouldn’t “play as God” through modifying genes, among other criticisms.


Despite increasing cancer rates, improvements in cancer treatment have been notable – exemplified by reduced mortality rates. Scientists continue to learn more about cancer and the human body. As researchers continue to create and discover new treatments, maybe one day, the idea of cancer being a fatal disease will be an outdated one.


Sources

https://medicine.missouri.edu/centers-institutes-labs/health-ethics/faq/gene-therapy


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