Health & Medicine

  • Issue 93 / May - June 2013



    Cancer: Cellular Anarchy

    Ali Fethi Toprak

    Cancer is a complex disease, claiming millions of lives every year. There is no single type of cancer. However, all types of cancer have one thing in common—anarchy. It is noteworthy and insightful to compare micro-worlds to macro-worlds to unearth life’s secrecies, like comparing “Anarchism” with “Cancer” to understand and develop approaches towards the treatment of cancer (Table 1). Anarchy is referred to as a political disorder or lawlessness within a society, often resulting from the accumulation of ideas and actions against the system that might lead to the collapse of the governance. Cancer is, on the other hand, defined as the loss of normal cellular growth that results from accumulated mutations, which leads to uncontrolled growth of cancer tissue, namely tumor.

    One of the signs of anarchy in a region could be the marching of an army to get a particular situation under control and, if it is indispensible, destroy or suppress anarchists. Similarly, the first response of the body to such uncontrolled growth is the destruction of tumor cells by activating inner mechanisms that lead to cellular suicide (apoptosis). Anarchy is by definition not to accept any border and authority, causing disorder or upheaval. According to twentieth century thinker Nursi, anarchy cuts and throws away norms and laws that organize social life, one by one, thus destroying the order and leading to mischief and rebellion. In addition, anarchism does not consider the rights of any. Analogously, one by one, cancer breaks genetic rules that organizes cell proliferation and eliminates pathways that suppress tumor formation. Thus, it eradicates the order and triggers chaos and malignancy. Again, cancer works against the life of the body without considering the rights of other cells.

    Another characteristic of anarchism could be the elimination of its leaders. Thus, once you get rid of the key players, anarchy may not resurface. Likewise, you can use a strategy in certain cancer types where you can specifically target cancer stem cells. As a result, cancer growth could be suspended and it may bring an opportunity to shrink tumor through chemotherapeutical approaches. One such example is the targeting of CD24, a putative cancer stem cell antigen expressed by a minority of adenocarcinoma cells. This cell-based cancer immunotherapy method uses genetically engineered cancer killing T cells, which are directed towards cancerous tissues using chimeric antigen receptors. This is similar to the taking over of trained Special Forces when anarchy becomes malicious and unceasing. Both natural and genetically engineered cancer killer T cells in our body resemble trained Special Forces that patients need to fight against cancer.

    Table 1

    Cancer treatments

    Cancer is nowadays mainly treated with chemotherapy, radiotherapy and surgery, and to some extent with immunotherapy. The many purposes of chemotherapy include relieving or preventing the suffering of the patient, prolonging the life span, and if possible, completely curing the cancer along with surgery or radiotherapy regimens. Chemotherapy mainly uses cytotoxic drugs that kill cells by attacking one of the main properties of cancer cells—rapid division. Unfortunately, since cancer cells are not the only rapidly dividing cells in the body, chemotherapeutic agents also harm healthy cells. Another fall back of chemotherapy drugs is the lack of specificity that does not provide a therapy against a specific cancer type and their efficacy vary from patient to patient. In these cases, the indispensable path is synergistic use of radiotherapy with chemotherapy.

    As its name implies, radiotherapy involves the use of ionizing radiation to kill cancer. It relies on the destruction of dividing cells by introducing DNA damage, which leads to induction of cellular death through apoptosis. Radiotherapy is therapeutically useful in cancers that are localized to one part of the body. It is also useful to prevent tumor relapse after surgical removal such as in breast cancer. However, radiation, which radiotherapy depends on, is itself the potential cause of cancer and leads to various side effects.

    Citizens of the body need justice
    Chemotherapy or radiotherapy, which harms both healthy and cancerous cells, recalls the practice of absolute justice versus relative justice. Absolute justice requires protection of every individual while punishing the criminals. On the other hand, relative justice is the justice where the rights of one person are ignored for the betterment of the whole. Absolute justice is always the best practice if it can be properly established. However, relative justice may be sought if absolute justice is absolutely out of reach. Current chemotherapy and radiotherapy treatments are like the practice of relative justice, which harms both cancerous and healthy cells. Of course, these treatments are considered as the last resort for many cancer patients but this analogy regarding absolute justice toward cells in the body urges us to seek for cancer therapies that follow absolute justice. In other worlds, we need to practice an approach that is more specific toward cancer cells. This could be, as we mentioned above, the use of cancer immunotherapy where cytotoxic T cells are directed towards cancer cells through genetic engineering by introducing chimeric antigen receptors (CARs). CARs should be able to recognize unique or relatively specific antigens located on the surface of cancer cells to execute them.

    Cancer killing T-cells: equipped with chimeric antigen receptors
    There are three main approaches in cancer immunotherapy including immunization, use of antibodies and cellular immunotherapy. Immunization by administering a cancer vaccine prepares the patient's own immune cells to recognize tumor cells as targets to be destroyed. The use of therapeutic antibodies specific to cancer cells recruits immune cells in the patient to abolish tumors. Cellular immunotherapy, on the other hand, uses patients’ own immune cells like the natural killer cells, cytotoxic T cells and so on. Basically, those cells could be stimulated in patients with the administration of interleukins or they could be isolated from the patients’ blood and cultured in the laboratory and following expansion and in vitro training, then transfused back to the patient to fight against cancer.

    Cytotoxic T cells are unique immune cells that recognize target cells via T cell receptors. Over the past decade, scientist engineered T cell receptors and developed chimeric antigen receptors that specifically recognize target antigens. This recognition lead to signaling pathways that resulted in apoptosis of tumor cell through the production of granzymes, perforins and cytokines such as IFN-γ, and TNF-α (Figure 1). There are a number of success stories using CAR+ T cells for cancer immunotherapy used in patients. Encouraging results were obtained with CARs targeting lymphoma (by targeting CD19 antigen), coleractal Cancer (by targeting CEA antigen), and melanoma (by targeting melanocyte-specific markers MART1, MELOE-1 and gp100).

    Resim

    Universal chimeric antigen receptors
    Two recent studies published by two different groups increased the hopes in the battle with cancer. They developed novel and universal CAR technologies that combines cell based immunotherapy and use of therapeutic monoclonal antibodies. This new approach relies on the recognition of specific molecules such as FITC and Biotin by corresponding Anti-FITC and Anti-Biotin (Avidin) CARs. The decent thing about these specific molecules is that you can attach them to any antibody, ligand, or aptamer known to target specific tumor antigens (Figure 2). One of the universal chimeric antigen receptor, for instance, uses FITC, a fluorescent molecule widely used in flow cytometric assays. Since it is easy to label antibodies, this provides wide range of antibodies to target cancer cells. In addition, scientists using this approach could target more than one tumor antigen or could use another antibody that targets different antigen even if cancer relapses. Moreover, since antibodies used to activate CAR+ T cells will degrade and their bioavailability will decrease in the body by time, there will be no need to kill injected T cells with suicide mechanisms. Once FITC labeled antibodies are stopped from being given to patients, CAR+ T cells will stop attacking cells and cease-fire since their guns (CARs) cannot recognize tumors or anything nonspecific. This approach is highly encouraging and has brought with it great hopes in the treatment of cancer.

    Resim

    Anarchy, spirituality, and prayer therapy
    Hunger, poverty, social inequality and economical issues could be asserted as the basis of anarchy within a society. However, according to Nursi, the real basis of anarchy is spiritual weakness and poverty. Similarly, the basis for cancer could possibly be the lack of appropriate spiritual diet that may eventually make a person fall spiritually and physically weak. For example, fasting is a physical and spiritual fast prescribed in monotheistic religions which increases spirituality and has been shown to be synergistically effective in chemotherapy with cancer treatments. It has been observed and scientifically recorded that patients with strong beliefs and continuous prayers and spiritual support overcome diseases much faster than those without. This raises certain questions regarding our spiritual makeup and many other dynamics involved in being sick and getting well. So, are we getting ill because some evil spirits are manipulating our biological condition by settling in the tumors and propagating cellular anarchy? Is radiation, which leads to cellular mutations, a result of spirits that are created of “scorching fire” (The Qur’an 15:27)? Is cancer a result of such manipulations and should we seek cure for it not only through biological medicine but also through spiritual healing?

    Various scientifically proven causes are known to increase the likelihood of cancer, which includes, but is not limited to, smoking, viral infections, radiation, and pollutants that lead to internal genetic faults within cells. Considering the fact that there are many cases in which patients have been reported to have recovered from their illnesses by reciting prayers, then such cases are worth examining to find out whether and to what degree non-material factors are involved as causes for our illnesses. Studying these cases may offer science new opportunities to be able to remove the present obstructions and make greater advances in the medical field by perhaps developing cancer therapies that combine prayer therapy and cancer immunotherapy using genetically engineered T cells during the treatment of patients.

    Ali Fethi Toprak is a PhD candidate at University of Texas Southwestern Medical Center.

    References

    Döğen, Şaban. 2005. “Bediüzzaman and Anarchy.” Köprü Dergisi, No 89.
    Nursi, Bediüzzaman Said. Işarâtü'l-I'caz. Şahdamar Yayınları.
    Chmielewski et al. 2012. “CAR’s made it to the pancreas.” OncoImmunology 1:8, 1387–1389.
    Tamada et al. 2012. “Redirecting Gene-Modified T Cells toward Various Cancer Types Using Tagged Antibodies.” Clin Cancer Res.
    Urbanska et al. 2012. “A universal strategy for adoptive immunotherapy of cancer through use of a novel T cell antigen receptor.” Cancer Res.
    Gülen. M. Fethullah. “Cinler, Hastalıklara Sebep Olabilir mi?” Retrieved from http://tr.fgulen.com/content/view/708/3/ on 12/24/12.
    Bukhari, i'tikâf 8, 11, 12; Muslim, Salam, 24; Ibn Maja, Siyam 65; Abu Dawud, Sawm 79; Adab 81; Muslim and related hadith narrated by Abu Hurayrah, Bukhari 7.582.

    1 See Yücel, Salih. 2010. Prayer and Healing in Islam, NJ: Tughra Books.

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