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 __(adding "be") treated as soon as possible or else run the risk of endangering their life. However, while conventional therapies are able to prolonging the lifespan (better to add "of the patients"), and in some cases, cure patients (them), 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 (about? suggest deleting) 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.
  3. To reduce interaction between the anti-tumor drug and normal tissues, as well as establishing a high local drug concentration, our drug-delivery bacteria will be designed to recognize cancer cells and target them specifically.
  4. Apart from delivery, our bacteria will work as a drug synthesis machine, producing anti-tumor drugs in a controllable manner.
  5. Regulatory systems will be introduced to internally and externally guiding the timing and dosage of drug delivery.

To achieve these objectives, three modules were developed: (please quote the actual name of proteins/systems in below sections when mentioned)

  1. Targeting module: Targeting of bacteria to tumor cells will be achieved through a tumor-specific binding peptide which was first discovered in a phage displaying selection (what sort of selection?). It will be expressed and displaying on the surface of bacteria with the aid of a cell wall binding system.
  2. Drug synthesizing module: An anti-tumor cytokine will be synthesized by the bacteria and secreted out to external environment (how?). As a signaling molecule, the anti-tumor cytokine represses the proliferation of tumor cells and arrests them in G1 phase (for all kinds of tumours? or just colon cancer. remember that you haven't mentioned your choice of cancer target yet).
  3. Regulation module: Two regulatory systems will be established in consideration of possible harm from uncontrolled drug release. An inducible system (what kind?) is set up to externally control the timing of drug secretion, while another 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 pursuing a universal cancer therapy, we choose to focus on colon cancer only for this project. Although colon cancer is not one of the most common cancers in the world, nor has it been well studied; several properties of colon cancer captured our interest and led us to conceive the whole project.

  1. Adenocarcinoma: adenocarcinoma is the most common type of colon cancer. It contributes to more than 95% of diagnosed cases ( Originating from rapidly dividing polyps (gland cells lining in bowel wall), they proliferate, protruding and eventually damaging epithelial cells in digestive tract, which usually results in bloody stool. The exposure of colon adenocarcinoma on the mucosal surface allows tumor cells access to the digestive tract, This particular feature allows us to employ the anti-tumor agent directly by targeting exposed tumor cells in the digestive tract, removing the need of circulating the drug through the body. This limits the spreading of drug molecules throughout body and to some extent reduces the adverse effects of drug treatment.
  2. Difficulty of diagnosis: Colon cancer is curable and preventable if it is diagnosed in early stage. However, early stage colon cancer is usually silent and the patient shows no symptoms, making it difficult to detect until it has progressed to more malignant stages. Therefore, in order to lower the prevalence of colon cancer and reduce its mortality rate, it is important to execute cost-efficient screening in patients who show no symptoms but are known to be at high risk for it. The use of bacteria with recognition peptides specific to colon cancer cells could serve as a detecting agent in colon tumor screening which causes minimal adverse effects and discomfort to the patient. (how do you detect the bacteria then?) Once colon tumor is detected, this bacteria can synthesize and produce anti-tumor molecules to kill or inhibit colon cancer cells specifically.