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Eukaryon

The Cancer Conundrum

Maddie Strejc
Lake Forest College
Lake Forest, Illinois 60045

       Cancer has had an immense impact on healthcare in America and around the world. Although this disease is well known, a cure is still far from reach, and billions of dollars have been invested in improving treatment . However, it is becoming more apparent that treating this deadly disease does not have one clear route. Cancer can especially turn deadly when cancer cells move from their original site to another area of the body, creating even more complications. As researchers turn their attention towards this lethal process known as metastasis, better treatment might be on the horizon.

       Even if a surgeon removes a tumor perfectly, cancer does not necessarily disappear along with it, as the tumor most likely had already disseminated thousands of cancer cells as early as the diagnosis. For breast cancer patients, these disseminated tumor cells (DTCs) often spread to the bone marrow. The presence of DTCs is usually indicative of metastasis, but not all DTCs cause metastasis. The ones that do are called metastatic stem cells or MetSCs, which are derived from cancer stem cells (CSC) that show migratory behavior. More research is needed to identify organs that can harbor these cells, but the good news is that removal of MetSCs is possible. However, they are often not removed entirely. If they are detected after therapy there is, unfortunately, a high chance of recurrence and poor survival.  These cells can survive so well because their nonproliferative state  renders them resistant to antimitotic therapy. (Oskarsson, Batlle, & Massagué, 2014). Withstanding the effects of therapy, the cells can reinitiate the growth of a tumor in distant tissues.

       Nevertheless, cancer stem cells do require very specific traits to survive in these distant tissues to begin the metastatic process. Certain mutations in pathways regarding epigenetic control favor the expression of metastatic traits in cancer cells. These mutations create issues through imbalances in cell growth, invasiveness, and cell renewal pathways rather than acting directly as oncogenic drivers. Additionally, metastatic seeding traits help these cells survive when they move to distant organs. CSCs also possess traits that help them survive stressful environments. This helps them persist at the invasive site where the growing tumor meets the stroma because here cells are exposed to several forms of distress such as hypoxia. There are also organ-specific seeding traits that prime CSCs for survival in specific areas distinct from the origin. The origin and distant site have very different characteristics relating to cellular composition and immune surveillance as cancer cells injected directly into a different site undergo apoptosis fairly quickly.  The probability that these CSCs will become MetSCs does not solely depend on whether the cells reach the distant site but also if they survive at that specific site, and that survival rate is relatively low.

       Although there is a seemingly small chance of survival for CSCs in areas of the body separate from the origin, researchers have identified “metastatic niches” that have the necessary components to support the survival of these cells. These niches promote self-renewal and are located in several organs throughout the body. Cancer cells are often able to occupy niches native to the foreign tissue including perivascular niches that supply oxygen, nutrients, and paracrine factors. Niches are also important for maintaining the self-renewal capacity of DTCs by activating vital pathways. Oddly enough, metastasis can lay dormant for years, which researchers have hypothesized is due to these niches that support DTCs. Unfortunately, during this latency period cancer cells can evolve and develop metastatic colonization functions they previously did not have. As DTCs constantly enter and exit the dormant state they “are more susceptible to being hijacked by MetSCs” (Oskarsson, Batlle, & Massagué, 2014).

       Cancer’s many intricacies have prevented researchers from finding effective and cancer-specific treatmentsfor years. Metastasis especially makes this disease deadlier as cancer cells disperse from the tumor the minute it has formed. Understanding this process is key to preventing the spread of cancer throughout the body. Understanding the traits that allow cancer cells to spread and proliferate throughout the body is critical in developing treatments to inhibit this process. This research has shed more light on MetSCs, which may lead to more therapeutic approaches focusing on suppressing metastasis. Ultimately, more research is needed to develop this promising avenue for treating cancer.

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Eukaryon is published by students at Lake Forest College, who are solely responsible for its content. The views expressed in Eukaryon do not necessarily reflect those of the College.

Articles published within Eukaryon should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.