As is well known, a singular treatment is not enough to eradicate cancer from the body. The older approach to treating cancer is with the use of chemotherapy, a nonspecific cytotoxic chemical, while the newer approach is to treat cancer with targeted and immunotherapy treatments which have the capability of specificity (Vanneman, Mathew, et al.). Chemotherapy kills all cells that produce rapidly, it is narrow spectrum, highly toxic, and resistance is known to occur quite frequently (Vanneman, Mathew, et al.). Because chemotherapy kills all highly prolific cells, this means that healthy cells are killed along with the cancerous cells. Chemotherapy, along with other conventional therapy methods, attack tumors and cancerous cells directly, while targeted therapy and immunotherapy do so indirectly (Rangel-Sosa, Martha, et al.). Targeted therapy blocks molecular pathways responsible for tumor growth and stability, and immunotherapy elicits an immune response and creates long term destruction of tumor cells (Vanneman, Mathew, et al.). One specific pathway targeted therapy block is oncogene addiction, which is “a process by which a single mutated gene or signaling pathway drives tumor proliferation” (Vanneman, Mathew, et al.). Targeted therapy also inhibits critical biochemical pathways and mutated proteins that stimulate tumor development, growth, and survivals; drugs have been used and prohibited disease development and increased regression in some cases (Vanneman, Mathew, et al.). In most cases, targeted therapy remission results are not permanent, just like with traditional chemotherapy. Since targeted therapy arrests tumor development and decreases a tumor’s suppression of the immune system, this provides an opportunity to utilize immunotherapy as well to create a greater cytotoxic effect against cancer cells. Combining treatment methods has been found to be helpful due to the diverseness of cancers, acquired resistance to medications, and the importance of individualized therapy. Combination is most efficient when each treatment is researched on how they interact with the immune system and what phase they begin working. Immunotherapy agents, radiation and chemotherapy dosage/type/duration, and any other therapeutic agents must work in synergy with each other and induce cohesive effects that play off of one another. For example, a combine therapy could include a suicide gene releasing tumor associated antigens that then recruit antigen presenting cells and T-regulatory cells. An immune checkpoint inhibitor could then suppress the T-regulatory cell activity and increase T-cell production. The T-cells produced and activated could then fight the tumor and create immune memory that would produce long-term tumor-lytic effects.
One study chose to look at rice bran arabinoxylan compound (RBAC) as an immunotherapy agent, and study its effects on cancer and the immune system when used in combination with chemotherapy. RBAC was found to be efficient at activating natural killer cell activity and eradicating cancer cells in-vitro and in-vivo (Jurasunas, Serge).
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RBAC is a nutritional additive, made by the enzymatic hydrolysis of hemicellulose B (a dietary fiber found in rice bran) (Jurasunas, Serge). Arabinoxylan is a highly complex sugar that is obtained by extraction from bran rice; the extraction process breaks down the long polysaccharide molecule into smaller, less complex ones (Jurasunas, Serge). Arabinoxylan in its normal form is far too complex for absorption, when it is broken down into simpler molecules it can be absorbed into the circulatory system and spread throughout the body. RBAC is the most robust biological response modifier because it is a risk-free compound with no toxic qualities, that does not lead to an immunotolerance (Jurasunas, Serge). The main purpose of this supplemental treatment was to affect the activity of natural killer cells. Natural killer cells are large granular lymphocytes and they are the first line of defense from foreign substances, and as we know now, cancer as well (Jurasunas, Serge). This is especially important for cancer patients because this study found that individuals with cancer have 50% to 70% less natural killer cell activity and number than normal individuals (Jurasunas, Serge). Natural killer cells also decrease in affinity and in number with age, this could possibly be a reason that cancer rates increase with age. It also means that the natural killer cells that elderly cancer patients to have left are not functioning at full capacity. So, essentially, the idea behind this study was that if they could increase the number and activity of natural killer cells, the immune system would be more effective at killing cancer cells. Natural killer cells play an important role in innate immunity, but they also bridge the gap between innate and adaptive immunity as well. Natural killer cells have activating and inhibitory receptors within their cell membrane that allow them to be activated by any antigen or foreign material without any prior sensitization, and they have the ability to amplify tumor-lytic responses (Jurasunas, Serge). This is why natural killer cells are said to provide an upper hand in the prevention and treatment of cancer. Natural killer cells differentiate and mature in bone marrow, lymph nodes, the spleen, tonsils, and the thymus; after maturation the enter circulation (Jurasunas, Serge). When at rest, natural killer cells monitor the circulatory and lymph systems, and when a foreign entity (a cancer cell in this case) is discovered, they exhibit cytotoxic qualities and attack the cell (Jurasunas, Serge). The first way that they attempt to kill cancer cells is by the release of cytotoxic granules in response to cytokines (Jurasunas, Serge). When a cancerous cell is found, the natural killer cell adheres itself to the surface of the cell via receptors, it then injects granules of perforin and releases granzyme serine protease; this causes apoptosis of the cancer cell due to DNA degradation (Jurasunas, Serge). Perforin is a membrane disrupting protein that opens up the cancer cell membrane, forming an opening that allows the protease to enter the cell (Jurasunas, Serge). After activation, and the initial ‘attack’, natural killer cells can induce apoptosis within the cancer cell in as little as five minutes, and the process can be repeated for approximately twenty-seven times before the immune cell becomes permanently inactive (Jurasunas, Serge). Natural killer cells in normal cancer patients are degranulated and deactivated, while natural killer cells in patients supplemented with RBAC show increased granular content and increased adhesion capability (Jurasunas, Serge). The study found that RBAC creates cell recognition through supplement immunoprofile, decreases antigen tumor markers, improves treatment, and increases lifespan compared to patients receiving chemotherapy only (Jurasunas, Serge). While natural killer cell activity after RBAC supplementation alone increases initially, reaches a plateau, and then slowly declines, the study found that the use of RBAC coupled with conventional treatment (such as chemotherapy) found the cause less recurrence, decreased mortality rate, and an overall improvement in quality of life after treatment (Jurasunas, Serge). In another study of cancer patients receiving RBAC supplementation along with chemotherapy, natural killer cell activity rose and the increased activity continued even after supplementation stopped; the immune activity was maintained for approximately five years (Jurasunas, Serge). Overall, RBAC has shown the potential to: increase efficiency of conventional cancer treatment, reduce tumor size, decrease metastatic lesions, decrease tumor markers, minimize adverse side effects, and increase the chance of extended remission when coupled with traditional treatment (Jurasunas, Serge). This seems like a medical revelation. Why is this practice not utilized in every single cancer case?
Cancer is the second leading cause of death in the United States. Metastatic lung cancer is the first leading cancer in mortality rate, and metastatic prostate cancer is the second (Janiczek, Marlena, et al.). Immunotherapy is specifically useful in treating metastatic conditions, but the hope is that certain immunological agents can be tailored to treat early and non-metastatic cases as well. This could potentially prevent the spread of the cancer before it is too late. One study took the unit cost of each immunological agent and its dosage to find the cost per treatment, and then took the cost per treatment times the treatment length to find the cost over time, by cancer type, for each immunotherapy treatment (Shih, Ya-Chen, et al.). Trastuzumab was found to cost $50,000 yearly, bevacizumab came out to be around $10,000 every eight weeks, and cetuximab cost $20,000 every eight weeks (Shih, Ya-Chen, et al.). Bevacizumab in combination with FULFIRI showed increased responsivity (from 35% to 45%) and increased the average survival rate by almost five months (Shih, Ya-Chen, et al.). Trastuzumab when coupled with chemotherapy showed to be 50% responsive, increased survival rate by five months, decreased the chance of remission, and reduced the death rate by more than half (Shih, Ya-Chen, et al.). As stated before, immunotherapy is an incredibly useful took in the fight against cancer, but it comes at a hefty cost. In 2004 it was predicted that immunotherapy treatments would increase the cost of treating cancer by more than 370 million dollars.
This is worth mentioning because the United States is an aging population, meaning the general population is living longer and there are more elderly individuals than there are younger individuals. Because of the fact that as you age the likelihood of getting cancer increases, if there are more elderly individuals within a population there will be more instances of cancer. More instances of cancer therefore result in an exponential increase in healthcare costs. Immunotherapy has proven itself as a treatment for cancer, but with it being the newest treatment available, the cost is still high. It is important as a society for these treatments to be available across the board. Underprivileged and/or those without health insurance are not likely to benefit from this treatment based on the costs associated with administration.
Immunotherapy is a game changer in the field of medicine in regards to cancer treatment. Further research could unlock the answer to a cure. If scientists can figure out how to recruit the immune system to aid in the attack of cancer cells, maybe they could figure out a way to get the immune system to completely eradicate the disease on its own. Chemotherapy and radiation are very toxic, and in most cases seem to be counterproductive. The purpose of chemotherapy and radiation is to kill off cancer cells, and while they do accomplish that goal, they also kill off large quantities of healthy cells. The trick with such treatments is to find the type and dosage that kills all of the cancer cells before it kills the patient. These treatments also cause extremely adverse side effects, such as fatigue, hair loss, nausea, bruising and bleeding, increased risk of infection, loss of appetite, weight loss, mood and behavioral changes, and nerve and muscle damage (Hadish, Cindy). While immunotherapy still comes with its fair share of risks and side effects, the flu-like symptoms involved do not compare to that of chemotherapy (Hadish, Cindy).
In conclusion, immunotherapy has already shown great promise as a cancer treatment, but with further research we can explore even more options (possible even a cure) and attempt to make it available to all demographics that are in need of treatment.
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