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 nightmare of patients because of its high incidence, mortality and low recovery rate. With an annual incidence of more than 12 million, cancer accounts for more than 7.6 million deaths each year. Once diagnosed as cancer, patients have to rely on conventional cancer therapies to extend their life. However, while prolonging the lifespan of patients, these traditional therapeutic ways inevitably bring adverse effects to patients and intensively reduce their quality of life.
Surgery and cryosurgery are engaged as the main approaches in type I cancer treatment. While Small superficial cancer cells are physically removed during surgery, normal tissues or sometimes even parts of the organ need to be removed as well to prevent the recurrence of cancer. The loss of organ and changes of physical conditions in body are suffered by patients and long recovery time is needed after surgery as well. 
Chemotherapy involves drugs which are circulated through blood vessels, reaching cancer cells, killing or inhibiting cancer cell growing. Since most of the drugs used in chemotherapy target cells which are highly divided, organ or system which involves active cell replacement will be affect at most. This will bring about problems say bleeding, anemia, hair loss, infections and etc. In addition,
Radiotherapy which relies on high energy of X-rays, gamma rays or charged particles, kills cancer cells by damaging their DNA. However, the potential damage of normal tissues around cancer cells can never be prevented. Temporary and chronic side effects will be suffered by patent. Meanwhile, patients also need to take the risk of induction of secondary tumor by radiation.

Our mission

Considering all limitations in conventional cancer therapy, we, 2012 HKUST igem team initiated our project and aimed to establish an alternative cancer therapeutic way using the idea of synthetic biology.
We would like to make a breakthrough in the following aspect of cancer therapy through our project:

  1. Providing a simple cancer therapeutic way that is more acceptable to patient
  2. Relieving patients’ pain during cancer treatment
  3. Treating cancer without affecting patients’ quality of life intensely.
  4. Minimizing adverse effects to patients throughout and after cancer treatment

Bearing these in mind, we stretch our project as the following:

  1. To release patients from stress and fear in surgery and radiotherapy, anti-tumor drug is going to be employed to combat with cancer.
  2. A new drug delivery system is thus decided to be established in bacteria which are used as a carrier, facilitating drug transportation.
  3. To reduce interaction between anti-tumor drug and normal tissues and establish a locally high drug concentration, our drug-delivery bacteria are 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. To be controllable, regulatory systems are introduced, internally and externally guiding the timing and dosage of drug delivery.

To achieve these, three modules require developing:

  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.