Integrated human practice is an important part throughout the whole project. Based on the advice and feedbacks from the interviewees and the society, the integrated human practice has constantly inspired us to push the project forward. On the other hand, we have also reciprocally shared our experience and knowledge with different communities and social groups.
In brief, we have carried out a number of comprehensive human practical activities, which proceeded step by step. First of all, we sought advice from experienced physicians and biomedical research experts to carry out the original design of the anti-cancer protein RTAC. Also, from their advice and our homework, we conducted surveys and educations on cancer-related biomedical topics, as well as forging alliance with other iGEM teams in terms of research. Next, we visited the pharmaceutical company and communicated with other teams and experts. From their feedbacks, we consolidated our drug delivery plan by employing engineered yeast. Finally, we consulted the staff of the Food and Drug Administration to ensure that our proposed therapeutic approach complies with the current laws and policies. The detail process is below.
With our aim to develop a novel cancer-targeted therapy, we started our human practice. The hospital is first-in-line to contact with patients, thus we chose the hospital as our first step to visit. We interviewed Dr. Liu, who is experienced in treating colorectal cancer, and enquired him about the current situation of cancer treatment. Targeted cancer therapy gains much attention in the recent years, however, traditional therapies, such as chemotherapy and radiotherapy, are still dominant, said Dr. Liu. He pointed out that the new-generation cancer treatment has two major issues: high cost and low resources, which leads to the status quo. Because anti-cancer targeted drugs cannot enter the medical insurance and China lacks the intellectual properties of many drugs, a substantial amount of patients are discouraged by the high cost. In addition, the available treatment resources for cancer-targeted therapy are lacking. By and large, there are limited numbers of approved targeted therapeutic drugs. And the development of targeted therapy requires the basic biomedical research and a lengthy period of clinical trials before entering the market. He also pointed out that the population are still lack of the understanding of cancer targeted therapy, which created the barrier for its broad use. But he was optimistic of the advance of cancer-targeted therapy and encouraged to explore new opportunities.
With Dr. Liu's suggestions, we consolidated our idea to independently develop a cancer targeting drug with wide applications. In addition, it is also very important to enhance cancer science popularization for the public, so that patients and their families can understand and accept targeted treatment schemes.
At the same time, we also have new questions: how to develop a targeted drug that is applicable to a wide population? And how to effectively popularize science related to cancer?
With these questions, we visited China Medical University again to interview Professor Cao, a leading expert in basic cancer research worldwide. Professor Cao endorsed our idea to develop novel cancer-targeted therapy. He emphasized that cancer-targeted therapies all came from the translation of molecular understanding of the cancers. Within a short period, it is impossible to fully dissect the cause of a specific cancer, but it is doable to design the therapy based on current knowledge. Because the complexity of cancer causes, he suggested that we need to start with a specific subtype of a common cancer, and then consider extending it to more types. As cancer research is rapidly renewed, he also recommended us to seek for the up-to-date research for potential candidate. So, what kind of cancer should we start with and which target should be appropriately promoted? We decided to search the literature to solve the problems.
Based on Prof. Cao’s advice, we organized all team members to carry out literature search. Among the vast number of literatures, a series of papers about colorectal cancer attracted our attention. We were deeply impressed by the rising incidence rate of CRC. In addition, we noted that approximately 10% of CRC cases are caused by excessive activation of RSPO1, while there is no effective targeted therapy against it. Beyond CRC, RSPO was also documented to cause a myriad of other cancers2. Thus, a novel targeted therapy against RSPO suits our goal well.
After group discussion, we decided to go with CRC and chose RSPO as the target.
See more in "Description".
While determining our experimental plan, we also prepared for social activities. In order to investigate the public in a scientifical manner, we interviewed Professor Gao, an epidemiologist. Professor Gao explained to us in detail the importance of data collection and analysis, and suggested that we could plan for a questionnaire to survey people's understanding of targeted therapy and popular science forms they are willing to accept.
We made two sets of questionnaires and invited more than 1,000 people from all walks of life to fill them out. We agree that the Internet has a wide coverage, so our questionnaire is disseminated electronically.
The first set of questionnaires was aimed to investigate people's attitudes towards cancer targeted therapy. The results of the questionnaire showed that most people do not know much about targeted therapy, but had a fair interest to know it. According to the questionnaire, the publicity methods suitable for the public, the middle-aged, the elderly and the youth are radio official account, community publicity and comic strip, respectively.
The second questionnaire was mainly planned to interrogate the public's understanding of colorectal cancer and intestinal health. The results showed that most people had insufficient awareness of intestinal health protection and colorectal cancer prevention, and were willing to accept popular science education.
Together, these questionnaires gave us clear feedback of the current situation of the public and prompted us to carry out systematic and effective scientific broadcasts.
Based on these findings, we conducted follow-up education. The project has carried out popular science activities for the general public, the middle-aged, the elderly and the youth to promote targeted therapy and intestinal health related knowledge. After the activities, we collected feedbacks which proved of the success of our education. For example, art works from the children said that they started to know the importance of intestinal health and they were also curious about the targeted therapy of cancer.
In order to expand the range of targeted people and extend the influence of our education, the idea to turn our knowledge into characters came into view. Fortunately, we have found several teams which also have such thoughts with similar intestinal-treating projects. Therefore, we participated in the intestinal alliance activities, carrying out science popularization firstly and producing a popular science manual of intestinal health afterward.
We contacted the directors of pharmaceutical companies in Shenyang to understand the production of targeted drugs. And Dr. Bo from Kexing Biopharmaceuticals is interviewed by us for his advice in drug industry. Dr. Bo mentioned many companies are currently developing multiple products to treat intestinal diseases, including colitis and colon cancer. He acknowledged that in recent years, cancer targeted drugs had great economic benefits. His company is collaborating with several hospitals for the clinical trials of novel cancer targeted drugs. Also, there are various kinds of probiotics used as drugs for intestinal disease prevention and treatment, specified by Dr. Bo.
From his interview, we further understood the great value of cancer targeted therapy in the
perspective of industry. Also, we were inspired to employ probiotic engineered microorganism as
carriers to deliver our targeted drug. Since engineered microorganism perfectly fits in the core
idea of synthetic biology, we decided to incorporate this great idea into our project. In the
meantime, we carried out popular science activities for synthetic biology.
See more in "Communication".
As proposing for cancer targeted therapy, we share the similar interest with LZU-CHINA team. We actively met up with their team members for enlightenment. They shared their opinions for choosing E.coli, as we discussed the tumor microenvironment and the targeting effect of probiotics. We also exchanged science popularization activities on synthetic biology and formulated the next cooperation plan.
After the exchange, our team got the better idea of the benefit and attentions using probiotics. We carefully evaluated our design of RTAC, and considered the commensal fungi as the perfect carrier. We thus decided to consult relevant experts in fungi research to refine the research scheme.
After hearing our story and thoughts, Professor Ding suggested us to use yeast as the carrier. He demonstrated the advantages and disadvantages of different kinds of yeast for us, and recommended that Saccharomyces Cerevisiae was the best option. This yeast strand is a model organism that has been fully understood and studied for decades and poses no hazard to human health. He also suggested several pathways that are frequently engineered in yeast for our information. Due to his expertise, we invited him to our team’s advisory board.
Next, we have the following questions to decide: what kind of yeast should we choose? What pathway is yeast used? And what signal molecules are selected?
Based on Prof. Ding’s mentoring and our literature search, we finally decided to use S. Cerevisiae
as the carrier to deliver RTAC. From the readings, we found the mating pathway could be a great
choice to reprogram, and we realized eATP as signal molecule can sense the tumor environment. Based
on this information, we proceeded with our design and experiment.
See more in "Design" and
“Results”.
After designing the engineered yeast which can express our RTAC, we consulted Yuxin Lu, a friend who is the advisor of SJTU-BioX-Shanghai about the feasibility of our project. He had raised a very serious bio-safety issue that if our engineered yeast is let out into the environment, how can we ensure it is 100 percent safe to the environment? This reminded us the necessity to consider the environmental influence. In general, the brewer’s yeast is not considered as a biohazardous or pathogenic microorganism in the environment. However, considering of any unexpected hazard, we decided to add a self-killing switch to completely resolve this issue.
Our team members called the Liaoning Provincial Drug Administration, interviewed government staff by telephone, and asked about the relevant laws and regulations related to the clinical application of anti-tumor drugs. After knowing that we were designing new targeted medicine, they were very pleased and showed us the data to illustrate how fast the targeted medicine have pushed the growth of the economy of their company. After introducing our design of RTAC, they analyzed our project by reviewing several laws about the industrialization of new drug. Plus, they encouraged us and recommended several national regulations on relevant indicators.
And we have learned relevant laws and regulations. The management indicators for rational clinical use of antineoplastic drugs should include:
（1） Implementation of anti-tumor drug grading management system;
（2） Limiting the use rate of use grade and general use grade antineoplastic drugs;
（3） Proportion of money spent on anti-tumor drugs;
（4） The rational rate and intervention rate of anti-tumor drug prescriptions;
（5） Number and reporting rate of adverse drug reactions of antineoplastic drugs;
（6） Monitoring of clinical application of antineoplastic drugs and reporting of relevant data.
1 Seshagiri, S. et al. Recurrent R-spondin fusions in colon cancer. Natsure 488, 660-664, doi:10.1038/nature11282 (2012).
2 Ter Steege, E. J. & Bakker, E. R. M. The role of R-spondin proteins in cancer biology. Oncogene 40, 6469-6478, doi:10.1038/s41388-021-02059-y (2021).