Team:HKUST-Hong Kong/Background and Motive
From 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 medical practitioners face. The few treatment methods we have are painful and successful treatment cases often lead to relapse. Globally, more than 12 million new cases are being diagnosed each year (see link) and 7.6 million deaths attributable to cancer were observed in 2008 (see link). 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 greatly 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. But healthy tissues comprising essential parts of the affected organ often need to be removed to prevent the recurrence of cancer. As a result, patients must recover over an extended period of time as the tissue damage severely affects the 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). Organs or systems that involve active cell division/replacement are likely to also be affected by such treatment. 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 meaning as a result patients might 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 of establishing an alternative method of cancer therapy by making use of a biological system. However few cancer types are conducive to being treated in such a way. We thus decided to focus our attention to colorectal cancer for reasons detailed below.
Colorectal cancer is not the most common cancer in the world and it has not been well studied. However 95% of diagnosed bowel cancer cases take the form of adenocarcinomas (epithelial tissue cancers). These present a unique opportunity for treatment using a biological method.
Early form bowel adenocarcinomas take the form of rapidly dividing polyps (growths of gland cells that line the bowel wall). Their proliferation eventually leads to damage of epithelial cells in the digestive tract, resulting in bloody stool. Adenocarcinomas on the mucosal surface comprise tumor cells exposed to the digestive tract.
This particular feature means an anti-tumor agent can be applied through the digestive tract, removing the need to circulate the drug through the body. We can use this feature to prevent the spread of drug molecules through the body and limit any adverse effects the drug may have.
The gut flora of humans comprises hundreds of species of bacteria that function in harmony with their human host. It is conceivable that one such species that operates harmlessly in our gut could be engineered to suppress the growth of colorectal adenocarcinomas 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:
- To create a simple cancer therapy that has less side effects for the patient
- To reduce patients’ pain during cancer treatment.
- To treat tumour(s) without greatly affecting patients’quality of life.
Bearing these in mind, we proposed the following plan for the design of our system:
- An anti-tumor drug is going to be employed to combat cancer cells, removing the need for surgery and radiotherapy.
- A new drug delivery system will be established using recombinant bacteria as the drug carrier.
- Our drug-delivery bacteria will be designed to specifically recognize and target cancer cells to reduce interaction between the anti-tumor drug and normal tissues.
- For added versatility our recombinant bacteria will also work to synthesize and excrete the anti-tumor drug in a manner we can control.
- Regulatory systems will be introduced to internally and externally guide the timing and dosage of drug delivery by the bacteria.
We decided to separate these objectives into three modules:
- Target Binding. This module will pursue identification and subsequent implementation of a method to target our drug-delivery bacteria at cancerous cells to reduce collateral damage.
- Anti-tumor Molecule Secretion. Work under this module will first involve selection of a suitable anti-tumor drug that can be produced via recombinant means. Mechanisms will then be designed for synthesis of the drug within our drug-delivery bacteria and subsequent secretion of the drug to the external environment.
- Regulation and Control. This module aims to construct 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/