In mass media, we are frequently informed about treatments to diseases like leukemia, lymphoma, and Crohn’s. But rarely do we hear: “We found a cure to cancer!” So, one may wonder: what makes curing cancer such a seemingly impossible task, and what distinguishes it from other diseases?
There is one fundamental reason why cancers are difficult to eradicate: these cells adapt and evolve in response to treatment (Fodale, Pierobon, Liotta & Petricoin, 2011). Thus, even if a treatment is initially effective, its impact starts to dwindle, since the biological components that it blocks eventually “re-wire” themselves to circumvent the treatment (2011).
Chemotherapy – a method of using drugs to attack malignant (harmful) cells – is performed on 67% of all cancer patients (“Chemotherapy,” 2014). Yet, these
drugs can be resisted by cancer cells (“House call: What is metastasis?,” 2016). For example, studies conducted by a group of scientists at the MD Anderson Cancer Center, which participates in therapeutic clinical research exploring novel treatments for cancer, show that cancer cells can travel to different parts of the human body, known as metastasis (2016). This makes it especially difficult to track down cancer cells and prevent them from spreading (2016). However, scientists have found that cancer cells use a protein called PGC-1a, which helps form new mitochondria, used to harness energy (Tan etal., 2016). Using this energy, they metastasize to different parts of the body and find a new home to live in, making it hard for scientists to track them down (2016).
Tumor cell expansion is further proliferated by its uncontrolled growth (Eales, Hollinshead & Tennant, 2016). Scientists have found that the deformed tumor blood vessels cause regions of hypoxia or oxygen-deprived conditions (2016). Hypoxia – a condition in which the body is deprived of adequate oxygen supply – arises in tumors through the rapid proliferation of cancer cells, which causes the tumor to exhaust the nutrient and oxygen supply from the normal blood vessels (2016). However, the tumor-proliferating effects of hypoxia cannot be generalized because they can either have detrimental or beneficial effects depending on severity, duration, and context (2016).
Yet there are even more ways that cancer cells can adapt: they manipulate an enzyme called PKM2 (Prescott, 2011). By keeping PKM2 levels low, the cancer cells channel incoming glucose to metabolic pathways that generate antioxidants, thereby surviving oxidative stress, the imbalance between the production of free radicals and the ability of the body to counteract their harmful effects (2011). Thus, it is hard for scientists to investigate PKM2 manipulation by cancer cells (2011).
Despite the adaptive nature of cancer, oncologists are continually learning more about cancer cells (Evan, 2014). For example, professor Gerard Evan, head of the Department of Biochemistry at the University of Cambridge, is studying the genes that drive the development and growth of cancer, called oncogenes (2014). To combat the disease, Evan uses genetically engineered mice, which enable him to toggle on and off tumor suppressor genes (2014). This allowed scientists to identify the most effective therapeutic targets and employ a range of molecular biology technologies to address roles played by key oncogene signaling pathways in the genesis and progression of cancers (2014). These technological advancements help develop effective treatments to combat the adaptive nature of cancer in the future.
- Brown, M.J. & Wilson, B. (2004). Exploiting tumor hypoxia in cancer treatment. Nature reviews: Cancer, 4, 437-47. 10.1038/nrc1367.
- Chemotherapy. (2014). Retrieved November 12, 2017, from https://www.health.harvard.edu/cancer/chemotherapy
- Evan, G. (2014). Determining the molecular basis of cancer. Retrieved August 12, 2017, from https://www.bioc.cam.ac.uk/people/uto/evan
- Fodale, V., Pierobon, M., Liotta, L., & Petricoin, E. (2011). Mechanism of cell adaptation: When and how do cancer cells develop chemoresistance? Cancer Journal (Sudbury, Mass.), 17(2), 89–95. http://doi.org/10.1097/PPO.0b013e318212dd3d
- Hollinshead , K., Tennant, D., & K., Eales. (2016). Hypoxia and metabolic adaptation of cancer cells. Oncogenesis, 5(190), 1-8. Retrieved November 12, 2017, from https://www.nature.com/articles/oncsis201550
- House call: What is metastasis? (2016). Retrieved December 9, 2017, from https://www.mdanderson.org/publications/oncolog/may-2016/house-call–what-is-metastasis-.html
- Prescott, B. (2011). Survival strategy of cancer cells . Retrieved November 12, 2017, from https://news.harvard.edu/gazette/story/2011/11/survival-strategy-of-cancer-cells/
- Tan, Z., Luo, X., Xiao, L., Tang, M., Bode, A. M., Dong, Z., & Cao, Y. (2016). The role of PGC1α in cancer metabolism and its therapeutic implications. Molecular Cancer Therapeutics, 15(5), 774-782. Retrieved December 9, 2017, from http://mct.aacrjournals.org/content/15/5/774