Circumventing Cancerous Circuits – Morning Sign Out at UCI

Written by Ashima Seth and Edited by Lauren Cho

Lung cancer cells. Credit: Anne Weston, Francis Crick Institute. CC BY-NC

Cancer is one of the most notorious of all modern diseases for its ability to circumvent the many proposed treatments that have been developed by researchers over the years. However, researchers at the University of Southampton may have recently found a possible remedy to prevent tumour growth. In order to understand how to cure cancer, however, we must first attempt to answer: what is cancer, and how does it develop?

Cancer is a disease that stems from genetic mutations that disrupt the cell cycle. Mutations that cause cancer are called carcinogenic and can be inherited or caused by exposure to radiation, smoking, and other various environmental factors. Carcinogenic mutations cause changes in the cell cycle mechanisms, particularly ones that control cell growth, differentiation and death (apoptosis). Cells that have undergone a carcinogenic mutation quickly multiply, forming lumps of undifferentiated cells called tumors which avoid apoptosis through a variety of means [1].

One of the ways in which cancerous cells avoid apoptosis is by creating what is commonly referred to in medical terminology as a microenvironment (the cellular environment in which the tumor exists). Cancerous tumours generally require more resources to sustain their uncontrolled growth; the need for additional resources increases as the tumors grow and spread. Thus, to increase supply of resources, cancerous cells induce cells of surrounding tissues to release biomolecules that then lead to the formation of new blood vessels in the region of the tumor, feeding cancerous cells with more oxygen and nutrients and transporting the cellular waste away from it [2]. The cancer study at the University of Southampton targeted this ability of tumors to create a microenvironment as a means of curing cancer.

There are several biomolecules associated with cancerous cells that help create a microenvironment. One of these is a complex known as HIF-1, which induces the formation of new blood vessels that cater to the tumor [3]. While past studies have attempted on eliminating HIF-1α and HIF-1β (two molecules that bind together to create HIF-1, but which, independently, are also crucial to cell function) altogether, researchers at the University of Southampton instead chose to engineer a genetic circuit that avoids the formation of the HIF-1 complex.

Initially, the study was focused on attempting to make a drug that consisted of a molecule that would prevent HIF-1α and HIF-1β from binding, essentially acting as an ‘open switch’ in the circuit. However, the research was then modified into actually coding this circuit modification into the DNA itself, and making the cell capable of monitoring its own HIF-1 production. A test in which such an engineered cell was introduced into a low-oxygen environment produced positive results, as the HIF-1 was not turned on [4].

While this study is a promising step further towards finding a concrete cure for cancer, there are several factors that will determine the success of this method. For one, there are several biomolecules that influence the sustenance of cancerous tumors , and there is no concrete evidence yet as to whether or not a modification in HIF-1 activity can have much of an effect on tumor growth. Secondly, even if HIF-1 does affect tumor growth, there is no knowledge yet as to which stage of cancer this treatment will be effective [5]. For answers to these questions, the effectiveness of this genetic circuit will likely have to be tested in an in-vivo environment (living system).

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