The article “Recent Developments in Targeting Carbonic Anhydrase IX for Cancer Therapeutics” discusses a new way in combating cancer cells, which is by targeting the enzyme carbonic anhydrase produced by these cancer cells. Carbonic anhydrase IX (CAIX) makes the production and growth of cancer cells favorable—first, it ensures that the intracellular pH is favorable for the growth of tumor cells then also makes the extracellular space acidic so that the tumor cells can spread more quickly. Therefore, interfering with or inhibiting the production of the CAIX enzyme can result in stopping the growth of the cancer cells themselves. This introduces a new way of combating cancerous cells; instead of killing the cells directly, the enzyme that is largely responsible for their production is targeted instead.
The CAIX enzyme is primarily induced by hypoxia, or the shortage in oxygen distribution among the tumor cells, triggering glycolysis. In order to overcome this, hypoxia-induced factor (HIF) 1α is then produced which then stimulates expression and production of proteins such as CAIX, among others (Dedhar, n.d.). In normal tissues, CAIX is highly inhibited, but it is overly expressed in cancer cells, as it is crucial for them to grow and develop. This was shown in the study conducted by Tan et al in 2009, which shows that CAIX is rarely found in normal breast tissue, but overly unregulated in breast tumor ones. Since CAIX helps cancerous cells to grow, then halting its production would mean that the cells cannot survive in the acidic environment brought about by the glycolysis due to hypoxia, and they would therefore die. One way to inhibit CAIX is to introduce compounds that bind to the CAIX site, thereby slowing down its production. Examples of such compounds include metoprolol, pentamidine isethionate, and Chembridge compounds #7653639 and #7633756 (Hovanky & Mehta, 2014).
The main drawback of this is that there are no sufficient animal models that are available to sufficiently study the effect of CAIX on cancerous cells. Furthermore, compounds that are developed to combat cancer have been largely focused on inhibiting extracellular proteins rather than intercellular ones. Fortunately, selective monoclonal therapies are beginning to take hold in clinical trials, and this may pave the way for experiments involving chemicals such as CAIX. This kind of cancer treatment can prove revolutionary to the battle against cancer as it involves nontoxic side effects.
References
Dedhar, S. (n.d.) Overcoming cancer: the critical role of CAIX. BC Cancer Agency Research. Retrieved from http://www.bccrc.ca/dept/ic/genetics/International%20Innovation%20p31-33_Shoukat_Dedhar.pdf
Tan, E. Y., Yan, M., Campo, L. Han, C.. Takano, E., Turley, H., Candiloro, I. Pezzella, F., Gatter, K.C., Milar, E. K. A., O Toole, S.A., McNeil, C.M., Crea, P. Segara, D., Sutherland, R. L., Harries, A.L., & S.B. Fox (2009). The key hypoxia regulated gene CAIX is upregulated in basal-like breast tumours and is associated with resistance to chemotherapy. British Journal of Cancer 2009 100. Retrieved from http://www.nature.com/bjc/journal/v100/n2/full/6604844a.html
Hovanky, V., & K. Mehta (2014). Carbonic Anhydrase IX Inhibitors: Finding potential therapeutic cancer agents through virtual screening. Journal of Young Investigators 27(2). Retrieved from http://www.jyi.org/wp-content/uploads//JYI_Aug2014_1to10-2.pdf
