Team:HKUST-Hong Kong/Background and Motive


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Team:HKUST-Hong Kong -


Conventional cancer therapies and their limitations

Cancer is gradually becoming the worst nightmare for the general public because of its increasing frequency of occurrence, painful treatments and relapse rate. More than 12 million new cases are diagnosed annually (around the world?), while accounting for more than 7.6 million deaths (percentage of total deaths?) each year. Once diagnosed with cancer, patients have to treated as soon as possible or else run the risk of endangering their life. However, while conventional therapies are able to prolonging the lifespan, and in some cases, cure patients, these traditional therapeutic ways inevitably bring adverse effects to patients and greatly reduce their quality of life.
Surgery and cryosurgery are the most direct forms of treatment for cancer. In this scenario, cancer cells are physically removed by surgery, but healthy tissues and sometimes even significant parts of the affected organ need to be removed to prevent the recurrence of cancer. As a result, patients often require extended recovery periods after surgery 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 thereupon kill or inhibit their growth. Most drugs used in chemotherapy target biochemical processes unique to rapidly dividing cells, and thus organs or systems that involve active cell division/replacement will likely be affect as well. This brings about side effects such as bleeding, anemia, hair loss and opportunistic infections.
Radiotherapy relies on high energy EM waves such as X-ray, gamma ray and charged particles to kills cancer cells by damaging their DNA. However, this treatment unavoidably damages normal tissues around cancer cells, and thus patients might suffer from temporary or even chronic side effects as a result. At the same time, this treatment also carries the risk of inducing secondary tumors by radiation damage.

Our mission

In view of all the limitations of conventional cancer therapies, our team initiated this project with the aim of establishing an alternative cancer therapy by taking advantage of the wonders of synthetic biology.
We would like to make a breakthrough in the following aspects of cancer therapy through our project:

  1. Create a simple cancer therapy that has less side effects for the patient
  2. Reduce patients’ pain during cancer treatment
  3. Treat the tumour(s) without greatly affecting patients’ quality of life
  4. Minimize adverse effects to patients throughout and after cancer treatment (<--repetition of previous pts)

Bearing these in mind, we proposed the following plan for our project:

  1. To relieve patients' stress and fear of surgery and radiotherapy, an anti-tumor drug is going to be employed to combat cancer cells.
  2. A new drug delivery system will be established using bacteria as carriers to facilitate drug transportation.
  3. To reduce interaction between anti-tumor drug and normal tissues and establish a high local drug concentration, our drug-delivery bacteria is designed to recognize cancer cells and target them specifically.
  4. Apart from delivery, our bacteria can work as a drug synthesis machine, producing anti-tumor drug in a controllable manner.
  5. In order to be controllable, regulatory systems are introduced, internally and externally guiding the timing and dosage of drug delivery.

To achieve these objectives, three modules are developed:

  1. Targeting module: Targeting of bacteria to tumor cells is designed to be achieved through a tumor specific binding peptide which is first discovered in a phage displaying selection. It is expressed and displaying on the surface of bacteria with the facilitation of a cell wall binding system.
  2. Drug synthesizing module: Employing an anti-tumor cytokine in our project, we design to have it synthesized by bacteria and secreted out to external environment. As a signaling molecule, the anti-tumor cytokine represses the proliferation of tumor cells and arrest them in G1 phase.
  3. Regulating module: Two regulatory systems are established in consideration of possible harm from uncontrolled drug releasing.  An inducible system is set up to externally control the timing of drug secretion. A toxin-antitoxin system is applied as well to minimize the adverse effects from over-dosage of the anti-tumor drug.

Why we focus on Colon cancer

Instead of investigating a universal cancer therapy, we choose to focus on colon cancer only this year. Colon cancer is not the most popular cancer in the world and neither has it been well studied. However, several properties and features of colon cancer promote our interest and prompt us to construct the whole project.

  1. Adenocarcinoma: adenocarcinoma is the most common type of colon cancer. It contributes to more than 95% cases ( Originated from highly dividing polys (gland cells lining in bowel wall), they proliferate, protruding and damaging epithelial cells in digestive tract which usually results in bloody stool. The exposure of colon adenocarcinoma on mucosal surface makes tumor cells accessible in digestive tract. This accessibility of colon tumor allows us to come up with this anti-tumor agent, which can target tumor cells in digestive tract without circulating in body fluid. The prevention of drug delivery through blood vessel eliminates the spreading of anti-molecules throughout body and to some extent minimizes the adverse effect from drug treatment. 
  2. Low diagnose rate: Colon cancer is curable and preventable if it is diagnosed in early stage. However, usually, colon cancer in early stage is silent without any symptom. Therefore, in order to lower the prevalence of colon cancer and reduce its mortality, it is important to execute cost-efficient screening in patients without symptoms or signs. The engagement of a bacteria anti-tumor agent with recognition peptide can right serve as a detecting agent in colon tumor screening which cause no adverse effects or even discomfort to the public. Once colon tumor is detected, this bacteria anti-tumor agent can synthesize and produce anti-tumor molecules to kill or inhibit colon cancer cells immediately.