Team:HKUST-Hong Kong/Background and Motive

From 2012.igem.org

Team:HKUST-Hong Kong - 2012.igem.org

Motive

Conventional Cancer Therapies and their Limitations

Cancer stands out as one of the most severe health issues today and is one of the toughest problems that medical practitioners face. The few treatment methods we currently have are painful and successful treatment cases often lead to relapse. Globally, more than 12 million new cases are being diagnosed each year (World Cancer Research Fund International 2012) and 7.6 million deaths attributable to cancer were observed in 2008 (World Health Organization 2012). Once diagnosed with cancer, patients have to be treated as soon as possible to increase their chances of survival. However, while conventional therapies are able to prolong the lifespan of patients, and in some cases, cure them, these traditional therapeutic methods have adverse effects on patients and reduce their quality of life.

Surgery and cryosurgery are the most direct forms of treatment for cancer. They involve the removal or destruction of cancer cells by physical means. Unfortunately, healthy tissues constituting essential parts of the affected organ often need to be removed together with the cancerous tissue to prevent recurrence. As a result, patients may require an extended period of time for recovery as the tissue damage severely affects the overall physical conditions of the body. 

Chemotherapy involves the use of drugs that, via blood circulation, reach cancer cells and kill or inhibit their growth. Most drugs used in chemotherapy target biochemical processes unique to rapidly dividing cells (rapid division is a key cancer cell trait). Unfortunately, this means that organs or systems that contain actively dividing cells are likely to also be affected by such treatment, and this leads to side effects that may include bleeding, anemia, hair loss and opportunistic infections.

Radiotherapy relies on high energy electromagnetic waves such as X-rays, gamma rays, and charged particles to kill cancer cells by damaging their DNA. However, this treatment unavoidably damages normal tissues around cancer cells, which means patients may suffer from temporary or even chronic side effects. At the same time, this treatment also carries the risk of inducing secondary tumors by radiation damage.

Focusing on Colorectal Cancer - Adenocarcinomas

In view of all the limitations of conventional cancer therapies, our team initiated this project with the aim to establish an alternative cancer therapeutic method by making use of a biological system. However, few cancer types prove to be suitable candidates for such treatment method. We thus decided to focus our attention on colorectal cancer for reasons detailed below.

95% of diagnosed bowel cancer cases take the form of adenocarcinomas (epithelial tissue cancers). These present a unique opportunity for treatment using our suggested biological method.

Early form of bowel adenocarcinomas take the form of rapidly dividing polyps (growths of gland cells lining the bowel wall). Their proliferation eventually leads to the damage of epithelial cells in the digestive tract, resulting in bloody stool.

Adenocarcinomas on the mucosal surface usually comprise tumor cells exposed to the digestive tract. This particular property means an anti-tumor agent can be applied from the digestive tract, removing the need to administer the drug through the circulatory system. This property may thus enable us to prevent the undesirable spread of drug molecules to the whole body, limiting any adverse effects the drug may have.

The human normal gut flora, which consists hundreds of bacterial species that coexist and function in harmony with each other and their human host. It is theoretically possible that one such species that operates harmlessly in our gut could be engineered to suppress the growth of colorectal adenocarcinoma cells by acting from the digestive tract. With these considerations in mind, we progressed to the next stage of project development.

Our Mission

We have the following goals for our project:

  1. To create a simple cancer therapy that has fewer side effects for the patient
  2. To reduce patients’ pain during cancer treatment.
  3. To treat tumour(s) without greatly affecting patients’ quality of life.

Bearing these in mind, we propose the following plan for the design of our system:

  1. An anti-tumor drug is going to be employed to combat cancer cells, hopefully removing the need for surgery and radiotherapy.
  2. A new drug delivery system will be established using recombinant bacteria as the drug carrier.
  3. Our drug-delivery bacteria will be designed to specifically recognize and target cancer cells to reduce interaction between the anti-tumor drug and healthy tissues.
  4. For improved safety, our recombinant bacteria will also work to synthesize and secrete the anti-tumor drug in a manner we can control.
  5. Regulatory systems will be introduced to internally and externally guide the timing and dosage of drug delivery by the bacteria.

To achieve the mentioned objectives, we decided to separate our project into three modules:

  1. Target Binding. This module pursues the identification and subsequent implementation of a method to target our drug-delivery bacteria specifically at cancerous cells.
  2. Anti-tumor Molecule Secretion. Work under this module first involves selection of a suitable anti-tumor drug that can be produced via recombinant means. Mechanisms would then be designed for the synthesis of the drug within our drug-delivery bacteria and subsequent secretion of the drug to the external environment.
  3. Regulation and Control. This module aims to devise and improve regulatory mechanisms that establish some control over the anti-tumor drug’s dosage and release time.

References

World Cancer Research Fund International. "Worldwide cancer statistics | WCRF." World Cancer Research Fund | Cancer Prevention Charity. N.p., n.d. Web. 26 Sept. 2012. http://www.wcrf.org/cancer_statistics/world_cancer_statistics.php

World Health Organization. "Cancer."WHO | Cancer.World Health Organization, n.d. Web. 26 Sept. 2012. www.who.int/mediacentre/factsheets/fs297/en/