Team:HKUST-Hong Kong/Background and Motive

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           <div><p align="center"><font size="20">MOTIVE</font></p></div>
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           <div><p align="center"><font size="20">Motive</font></p></div>
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               <h1>Conventional Cancer Therapies and their Limitations</h1>
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               <h1><p>Conventional Cancer Therapies and their Limitations</p></h1>
           </div>
           </div>
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           <p>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 diagnosed each year with 7.6 million of these cases resulting in  death. 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 prolonging 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. <br>
+
           <p>Cancer stands out as one of the most severe health issues today and is one of the toughest problems that medical practitioners face. The few treatment methods we currently have are painful and successful treatment cases often lead to relapse. Globally, more than 12 million new cases are being diagnosed each year (World Cancer Research Fund International 2012) and 7.6 million deaths attributable to cancer were observed in 2008 (World Health Organization 2012). 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 reduce their quality of life.   <br>
-
<br>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.  <br />
+
<br>Surgery and cryosurgery are the most direct forms of treatment for cancer. They involve the removal or destruction of cancer cells by physical means. Unfortunately, healthy tissues constituting essential parts of the affected organ often need to be removed together with the cancerous tissue to prevent recurrence. As a result, patients may require an extended period of time for recovery as the tissue damage severely affects the overall physical conditions of the body. <br>
-
  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. <br />
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  Radiotherapy relies on high energy EM (better to give its full name) 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. </p>
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<br>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). Unfortunately, this means that organs or systems that contain actively dividing cells are likely to also be affected by such treatment, and this leads to side effects that may include bleeding, anemia, hair loss and opportunistic infections. <br>
 +
 
 +
<br>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, which means patients may 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. </p>
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               <h1>Our mission</h1>
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               <h1><p>Focusing on Colorectal Cancer - Adenocarcinomas</p></h1>
           </div>
           </div>
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           <p><p>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.<br />
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           <p><p>In view of all the limitations of conventional cancer therapies, our team initiated this project with the aim to establish an alternative cancer therapeutic method by making use of a biological system. However, few cancer types prove to be suitable candidates for such treatment method. We thus decided to focus our attention on colorectal cancer for reasons detailed below. <br />
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   We would like to make a breakthrough in the following aspects of cancer therapy through our project:</p>
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<br>95% of diagnosed bowel cancer cases take the form of adenocarcinomas (epithelial tissue cancers). These present a unique opportunity for treatment using our suggested biological method.<br>
 +
<br>Early form of bowel adenocarcinomas take the form of rapidly dividing polyps (growths of gland cells lining the bowel wall). Their proliferation eventually leads to the damage of epithelial cells in the digestive tract, resulting in bloody stool.  <br>
 +
<br>Adenocarcinomas on the mucosal surface usually comprise tumor cells exposed to the digestive tract. This particular property means an anti-tumor agent can be applied from the digestive tract, removing the need to administer the drug through the circulatory system. This property may thus enable us to prevent the undesirable spread of drug molecules to the whole body, limiting any adverse effects the drug may have. <br>
 +
<br>The human normal gut flora, which consists hundreds of bacterial species that coexist and function in harmony with each other and their human host. It is theoretically possible that one such species that operates harmlessly in our gut could be engineered to suppress the growth of colorectal adenocarcinoma cells by acting from the digestive tract. With these considerations in mind, we progressed to the next stage of project development.<br>
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</p>
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              <h1><p>Our Mission</p></h1>
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          </div>
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          <p>
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   We have the following goals for our project:</p>
<ol>
<ol>
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   <li>Create a simple cancer therapy that has less side effects for the patient</li>
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   <li>To create a simple cancer therapy that has fewer side effects for the patient</li>
-
   <li>Reduce patients&rsquo; pain during cancer treatment</li>
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   <li>To reduce patients’ pain during cancer treatment.</li>
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   <li>Treat the tumour(s) without greatly affecting patients&rsquo; quality of life </li>
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   <li>To treat tumour(s) without greatly affecting patients’ quality of life.</li>
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   <li>Minimize adverse effects to  patients throughout and after cancer treatment (<--repetition of previous pts)</li>
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   </ol>
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</ol>
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<p>Bearing these in mind, we propose the following plan for the design of our system:</p>
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<p>Bearing these in mind, we proposed the following plan for our project:</p>
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<ol>
<ol>
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   <li>To relieve patients' stress and fear of surgery and radiotherapy, an anti-tumor drug is going to be employed to combat cancer cells.</li>
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   <li>An anti-tumor drug is going to be employed to combat cancer cells, hopefully removing the need for surgery and radiotherapy.</li>
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   <li>A new drug delivery system will be established using bacteria as carriers.</li>
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   <li>A new drug delivery system will be established using recombinant bacteria as the drug carrier.</li>
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   <li>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.</li>
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   <li>Our drug-delivery bacteria will be designed to specifically recognize and target cancer cells to reduce interaction between the anti-tumor drug and healthy tissues.</li>
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   <li>Apart from delivery, our bacteria will work as a drug synthesis machine, producing anti-tumor drugs in a controllable manner.</li>
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   <li>For improved safety, our recombinant bacteria will also work to synthesize and secrete the anti-tumor drug in a manner we can control.</li>
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   <li>Regulatory systems will be introduced to internally and externally guiding the timing and dosage of drug delivery (by the bacteria).</li>
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   <li>Regulatory systems will be introduced to internally and externally guide the timing and dosage of drug delivery by the bacteria.</li>
</ol>
</ol>
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<p>To achieve these objectives, three modules were developed: (please quote the actual name of proteins/systems in below sections when mentioned)</p>
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<p>To achieve the mentioned objectives, we decided to separate our project into three modules:</p>
<ol>
<ol>
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   <li>Targeting module: Targeting of bacteria to tumor cells will be achieved through a tumor-specific binding peptide which was first (better to use "previously" instead of "first" since it was not done by us) 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. </li>
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   <li><strong>Target Binding.</strong> This module pursues the identification and subsequent implementation of a method to target our drug-delivery bacteria specifically at cancerous cells. </li>
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   <li>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).</li>
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   <li><strong>Anti-tumor Molecule Secretion.</strong> Work under this module first involves selection of a suitable anti-tumor drug that can be produced via recombinant means. Mechanisms would then be designed for the synthesis of the drug within our drug-delivery bacteria and subsequent secretion of the drug to the external environment.</li>
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   <li>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 (better to use "the" or "an additional" toxin-antitoxin system is applied as well to minimize the adverse effects from over-dosage of the anti-tumor drug. </li>
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   <li><strong>Regulation and Control.</strong> This module aims to devise and improve regulatory mechanisms that establish some control over the anti-tumor drug’s dosage and release time. </li>
</ol></p>
</ol></p>
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               <h1>Why we focus on Colon cancer</h1>
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               <h1><p>References</p></h1>
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          </div>
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          <p><p>Instead of pursuing a universal cancer therapy, we choose to focus on colon cancer only (better to delete "only" and indicate that we just use the colon cancer as model to demonstrate our concept) 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.</p>
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<ol>
+
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  <li>Adenocarcinoma: adenocarcinoma  is the most common type of colon cancer. It contributes to more than 95% of (adding "the") diagnosed cases  (http://cancerhelp.cancerresearchuk.org/type/bowel-cancer/about/types-of-bowel-cancer).  Originating from rapidly dividing polyps (gland cells lining in bowel wall), they  proliferate, protruding (protrude) and eventually damaging (damage) 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 (the) 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.  </li>
+
-
  <li>Difficulty of diagnosis: Colon cancer is curable and preventable if it is diagnosed in early stage. However, early stage colon cancer is usually silent (to say disease is silent,appropriate?)and the patient(s) shows(show) 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 (better to say testing?) in (the) patients (already regarded as "patients" in this stage?) 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 (If I remember correctly, the secretion of BMP-2 is controllable externally, then how could this "automatic" process work?....).</li>
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</ol></p>
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           </div>
           </div>
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          <p>World Cancer Research Fund International. "Worldwide cancer statistics | WCRF." <em>World Cancer Research Fund | Cancer Prevention Charity. </em>N.p., n.d. Web. 26 Sept. 2012. <a href="http://www.wcrf.org/cancer_statistics/world_cancer_statistics.php">http://www.wcrf.org/cancer_statistics/world_cancer_statistics.php</a><br>
 +
 +
<br>World Health Organization. "Cancer."<em>WHO | Cancer.</em>World Health Organization, n.d. Web. 26 Sept. 2012. <a href="http://www.who.int/mediacentre/factsheets/fs297/en/">www.who.int/mediacentre/factsheets/fs297/en/</a>
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Latest revision as of 22:27, 26 September 2012

Team:HKUST-Hong Kong - 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 that medical practitioners face. The few treatment methods we currently have are painful and successful treatment cases often lead to relapse. Globally, more than 12 million new cases are being diagnosed each year (World Cancer Research Fund International 2012) and 7.6 million deaths attributable to cancer were observed in 2008 (World Health Organization 2012). 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 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. Unfortunately, healthy tissues constituting essential parts of the affected organ often need to be removed together with the cancerous tissue to prevent recurrence. As a result, patients may require an extended period of time for recovery as the tissue damage severely affects the overall 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). Unfortunately, this means that organs or systems that contain actively dividing cells are likely to also be affected by such treatment, and 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, which means patients may 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 to establish an alternative cancer therapeutic method by making use of a biological system. However, few cancer types prove to be suitable candidates for such treatment method. We thus decided to focus our attention on colorectal cancer for reasons detailed below.

95% of diagnosed bowel cancer cases take the form of adenocarcinomas (epithelial tissue cancers). These present a unique opportunity for treatment using our suggested biological method.

Early form of bowel adenocarcinomas take the form of rapidly dividing polyps (growths of gland cells lining the bowel wall). Their proliferation eventually leads to the damage of epithelial cells in the digestive tract, resulting in bloody stool.

Adenocarcinomas on the mucosal surface usually comprise tumor cells exposed to the digestive tract. This particular property means an anti-tumor agent can be applied from the digestive tract, removing the need to administer the drug through the circulatory system. This property may thus enable us to prevent the undesirable spread of drug molecules to the whole body, limiting any adverse effects the drug may have.

The human normal gut flora, which consists hundreds of bacterial species that coexist and function in harmony with each other and their human host. It is theoretically possible that one such species that operates harmlessly in our gut could be engineered to suppress the growth of colorectal adenocarcinoma cells 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:

  1. To create a simple cancer therapy that has fewer side effects for the patient
  2. To reduce patients’ pain during cancer treatment.
  3. To treat tumour(s) without greatly affecting patients’ quality of life.

Bearing these in mind, we propose the following plan for the design of our system:

  1. An anti-tumor drug is going to be employed to combat cancer cells, hopefully removing the need for surgery and radiotherapy.
  2. A new drug delivery system will be established using recombinant bacteria as the drug carrier.
  3. Our drug-delivery bacteria will be designed to specifically recognize and target cancer cells to reduce interaction between the anti-tumor drug and healthy tissues.
  4. For improved safety, our recombinant bacteria will also work to synthesize and secrete the anti-tumor drug in a manner we can control.
  5. Regulatory systems will be introduced to internally and externally guide the timing and dosage of drug delivery by the bacteria.

To achieve the mentioned objectives, we decided to separate our project into three modules:

  1. Target Binding. This module pursues the identification and subsequent implementation of a method to target our drug-delivery bacteria specifically at cancerous cells.
  2. Anti-tumor Molecule Secretion. Work under this module first involves selection of a suitable anti-tumor drug that can be produced via recombinant means. Mechanisms would then be designed for the synthesis of the drug within our drug-delivery bacteria and subsequent secretion of the drug to the external environment.
  3. Regulation and Control. This module aims to devise and improve 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/