Team:HKUST-Hong Kong/Background and Motive

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

BACKGROUND AND MOTIVE

Conventional cancer therapies and their limitations:

Cancer has gradually become 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. [1] Once diagnosed as cancer, patients have to rely on conventional cancer therapies to extend their life. However, while prolonging the lifespan of patient, 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 engages drugs which are circulated through blood vessel, reaching cancer cell, killing or inhibiting cancer cell growing. Since most of the drugs used in chemotherapy targets 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 tissue around cancer cells can never be eliminated. Temporary side effect and chronic side effect will be suffered by patent. Meanwhile, patient still also need to take the risk of induction of second 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 effect 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 tissue 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 situation.
  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 cell 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 effect from anti-tumor drug over-dosage.