Why are we focus on the topic cancer treatment?
1. An master's dissertation — Cancer Patients’ Seeking Survival in Epidemic Area
In the beginning of 2020, COVID-19 occurred in China. We closely followed the treatment of patients infected with the COVID-19. At this time, a graduate thesis in Journalism and Communication at Nanjing University caught our attention. This paper described the difficulty of cancer patients during the epidemic, which let us focus on the minority group during the epidemic—cancer patients. When medical resources are focused on treating cases of COIVD-19, cancer patients are facing more severe conditions than usual.
Figure 1. The Thesis
2. The interview with the author
Knowing that she is our senior sister, we immediately got in touch with her. Through the communication with her, we learned about the more specific experiences and difficulties of cancer patients. At the same time, she told us that we must be sincere and empathetic when communicating with patients. What impressed us was that she said: "You are listening to the story, and we are living a life." And such a tragic life is their real life...
Figure 2
3.search more information on the situation of cancer patients in the epidemic
After the discussion with Wang Tingting, we knew more about the difficulties cancer patients are faced with. Then a questions entered our minds: “Is this problem universal?" We collected information about the cancer treatment situation during the epidemic all over the world to answer this question. The following is what we got.
As of 8 am July 31, 2020 (GMT+8), there have been 17,106,007 confirmed cases of COVID-19 globally, with 668,910 deaths. According to a report released by the World Health Organization on 1st June, prevention and treatment services for non-communicable diseases have been severely affected since the start of the COVID-19 pandemic. Among the 155 countries surveyed, 42% had partial or complete disruption of cancer treatment; 58% of countries are now using telemedicine to replace in-person consultations; In 20 percent of countries, treatment for non-COVID-19 diseases has been interrupted mainly due to a shortage of medicines, diagnostics and other technologies.
United States
The state of response varies from state to state and from hospital to hospital in the United States. The vast majority of hospitals choose telephone consultation to fill the hollow period of cancer treatment. But many cancer patients still do not get timely treatment, with treatment delayed in about 27 percent of cases.
Western Europe
In the initial period of control, about 40% of patients' treatment was put on hold, and some institutions dedicated to helping cancer patients recover also ran into difficulties in capital turnover. Because the virus is more lethal to cancer patients, some countries worry that aggressive treatment contradicts the government's call for self-isolation.
Finland
The epidemic situation in Finland is not very serious and the medical level is high, so cancer patients are less affected.
Switzerland
The level of medical care in Switzerland is also high, and hospitals are better able to deal with the impact of the epidemic on cancer treatment.Some hospitals continue to treat cancer patients during the epidemic by means of remote diagnosis and treatment, mailing oral anticancer drugs and transferring cancer patients.But this method still causes inconvenience to patients and hospitals.
Italy
As the first country to report the epidemic in Europe, Italy is faced with the difficulties of blockade and openness.During the epidemic, most cancer treatments were put on hold, with data showing a 22 percent mortality rate among cancer patients in need of urgent surgery due to delays in some operations.Faced with outbreaks in hospitals, most patients have been asked to be treated at home.
Greece
Greece was less affected by the epidemic, and the initial measures were more stringent. In some Greek villages, the price of chemotherapy drugs has grown rapidly, and the return visits of cancer treatment that needs regular testing have been cancelled so cancer patients are less aware of their current condition. At the same time, due to the epidemic, Greece was forced to cancel about 7500 cancer operations every week at the beginning of the epidemic, and about 34.8% of patients could not be hospitalized.
South Africa
South Africa is the most severely affected area in Africa. Because of the epidemic, many surgeries have been postponed (some areas even reached 13,000), and medical costs have continued to rise with the shortage of resources. Due to the government's isolation policy, some cancer inpatients cannot receive care from their family members, and their psychology and physiology have suffered a double blow.
Australia
At the beginning of the epidemic, the Australian government adopted a strict epidemic level transfer rules. At the most severe moment of the epidemic, 90% of doctors were recruited from various positions for epidemic control and testing. This medical shortage lasted for nearly a month, and it was not until April 21 that the doctors who had been transferred were returned to their original positions after the epidemic in Australia stabilized. During the epidemic, some doctors were diagnosed with covid-19 causing delays in cancer treatment, so the Australian Cancer Center began to use telemedicine services to help treat the patients.
Japan
The National Cancer Research Center of Japan first compiled information related to the COVID-19 epidemic and published it on its official website. It gave the patients instructions, such as those who are receiving anticancer agents, which belong to the group with low resistance, and which are also vulnerable to severe disease, should avoid contiguity and assembly occupancies, wear masks well, and wash their hands often. Whether to delay their treatment depends on the type of cancer and the condition of their body. It is not yet clear when the epidemic outbreak will subside. It is recommended that treatment should be carried out as scheduled as far as possible. However, patients should not make decisions by themselves about whether to delay or cancel their tests or treatments, but should call the attending doctor for consultation.
India
Patients need to be tested to be COVID-19 negative before they can be treated. However, testing is lacking and in many places those who show non-infectious symptoms cannot be detected.
Brazil
A while back in severe epidemic outbreak, the hospital accepted only coVID-19 patients, and treatment for other diseases would be delayed. Brazilian hospitals are now fully open, but some medical insurance service require long queues that make it difficult to get a doctor. (Medical insurance in Brazil is not national; it is local or private.)
China
The epicenter of the previous epidemic only accepted severe cancer patients, and strict testing and epidemic prevention were required. The treatment of some patients was shelved.
In summary, the difficulties encountered in cancer treatment during the epidemic include: 1. the shift to drug-based cancer treatment, which has led to an increase in the price of drugs; 2. unclear diagnosis of cancer due to telemedicine; 3. the susceptibility of cancer patients to COVID-19 and the governments’ mobilization of medical resources to combat the epidemic, which has delayed cancer treatment and led to an increase in cancer mortality rates; 4. in some developing countries, it can also makes detection and access difficult due to inadequate state social welfare and low levels of medical care; 5. Cancer treatment in hospitals carries the risk of being diagnosed with COVID-19.
"If you've been doing cancer-related work long enough, you’ll understand that cancer is never just a scientific or medical thing...but an epidemic, for a specific family, a corner of the earth, can sometimes bring heartbreak, loss, and even desperate secondary disasters."
The advent of the epidemic has given us a better understanding of the problems in cancer diagnosis and treatment, so it is the intent of our project to take a practical approach to finding better cancer treatments.
How can an idea become a project?
Part 1
After we communicated with our PI-Chen Xi that we wanted to do projects related to cancer treatment, he suggested that we listen to a lecture on targeted therapy by instructor Fu Zheng -we got the idea of in vivo self-assembled small RNA.
We thought it’s pretty cool and self-assembled long effectiveness. So we decided to use a vector that can be stably transfected in the body for a long time: lentivirus to realize our project, which means it is hospital free!
Part 2
After we have a preliminary design for the project, we hope to discuss with relevant doctors and professors to see their thoughts on our project.
First of all, we chose Dr. Liu Rui from Tianjin Medical University Cancer Hospital. She expressed affirmation of our idea of combined treatment of three targets, and combined with the current dilemma of cancer treatment-the strong side effects of radiotherapy and chemotherapy, she pointed out that we hope that our project can ensure effectiveness while paying attention to safety.
Through the interview, we changed our goal from a hospital-free treatment to a safe and effective treatment which is closer to demand.
Part 3
So what can we do to improve our project? We interviewed Dr. Wang Rui from the General Hospital of the Eastern Theater Command. He believes that our method of choosing exosomes to encapsulate targeted therapy drugs has the characteristics of good compatibility and low toxicity, and meets the safety requirements; but he questioned the efficiency of exosomes packaging.
Figure 6
In order to solve this problem, we consulted various literatures and selected KIBRA protein to suggest the packaging efficiency of exosomes.
Figure 7
Part 4
After that, we further hoped that the professor would provide opinions on our project from the professional field, so we contacted teacher Li Rutian from NJU. She also thought that our joint drug delivery idea was very valuable and promising, but pointed out that our transformation of liver cells may be harmful to the function of liver and other body cells are adversely affected. So we added a Dox control switch, so that the entire project can only run when Dox is administered.
Figure 8
Figure 9
Part 5
Finally, we interviewed Huang Zhaohui from Jiangnan University. He questioned the efficiency of our lentivirus transfection and thought that we could replace the vector. At the same time, he believes that we need to verify that the siRNA produced by liver cells has an acceptable range of toxic and side effects. These two points are also improvements we hope to make in the second year of the project.
Figure 10
After discussion with doctors and professors, we formed our project. The project is divided into three parts to realize the functions of safety, effectiveness mentioned by professors and doctors.
Can our project become reality?
1. Questionnaire – test our project on a larger scale
In order to see whether our project is desired in the real world, we designed a questionnaire to know the factors to consider in actual cancer treatment and the application of elements relevant to our project, which is as follows:
① The subjects of our questionnaire survey are college students / researchers who have a certain understanding of biology.
② The questionnaire received 51 complete information, including 11 undergraduates, 17 postgraduates, 16 doctoral students and 7 other research workers. The age distribution was mainly 18-45 years old.
③ Most of the respondents had some knowledge of synthetic biology (≥ 84%), but less about iGEM.
④ We try to make the questionaire think about the treatment strategies they will do in the face of cancer from two different perspectives of doctors and patients. Compared with doctors, patients will be more disgusted with the current commonly used radiotherapy and chemotherapy, and choose the traditional Chinese medicine therapy with less body stimulation. This also reflects that patients are more willing to treat cancer in a stable way, while doctors pay more attention to curative effect.
⑤ However, doctors and patients show great consistency in the degree of emphasis on the advantages of cancer therapy; the killing effect on the target tumor (efficacy) and weak lethality (side effects) on other normal tissues are considered to be the two most important aspects in a cancer treatment method.
⑥ Among the characteristics of the new generation of cancer treatment drugs: drug resistance, cheap, convenient postoperative treatment, and durable. Convenient postoperative treatment is considered to be the most important issue, followed by drug resistance (the higher the score, the more important). Good efficacy, resistance to drug resistance and prolonged survival time were the three reasons that respondents used most to explain their own ranking.
⑦ Exosomes encapsulated siRNA is considered to be a very new field. In all the questionnaires, about 66% of the respondents knew about siRNA therapy and 60% of the respondents knew about exosomes for cancer treatment.
The above figure shows that researchers who know exosomes are more optimistic about the application of exosomes in cancer treatment. Most researchers think that the killing power of exosomes in treating tumors can reach 50% - 75%.
⑧ Although our project plans to use lentivirus as a vector to modify liver cells, so as to use the exosomes produced by hepatocytes to load tumor inhibitors independently to kill tumor tissues, most researchers believe that it is more reasonable to use plasmids to directly transform liver cells.
⑨ At the same time, more than 60% of the respondents thought that tail vein injection was a better way to achieve the transformation of rat hepatocytes, and suggested that we should not design more than 5 plasmids.
⑩ Finally, we listed several common gene mutation sites in NSCLC (non-small cell lung cancer). We tried to let the respondents choose a combination of several siRNA to treat the above mutation sites with iRNA, and collected their reasons for such selection (the next choice is for more than 10 people). Star protein, more mutations in non-small cell lung cancer, and new research hotspots are the three most common reasons.
The conclusion from the questionnaire is as follows:
· Patients are more willing to treat tumors in a way that does less harm to themselves, while doctors are more concerned about whether the efficacy is good.
· The new generation of anti-cancer drugs need to be combined with traditional cancer treatment methods such as surgery, which can help each other to produce better results, which is the common goal of current researchers. At the same time, how to solve the common phenomenon of drug resistance in cancer and prolong the survival time of patients is also an important topic.
· Our approach to targeting cancer with siRNA encapsulated in exosomes is very novel, and researchers have a relatively optimistic attitude towards our idea.
· Although we are currently designing to use lentivirus to transfect hepatocytes, the researchers believe that it may be better to use plasmids directly. We will change the project in the next year and try to compare the advantages and disadvantages of the two methods
· The three targets (KRAS, CD47, PD-L1) selected by our project are all the targets that researchers attach importance to and consider to be promising. We will continue to focuse these three targets to verify their combination in the treatment of NSCLC.
2. Shanghai Genechem Co., LTD – an attempt to future application
In light of the above, we thought that our design can be applied to some extent to actual cancer treatment, so we set out to interview relevant professionals for further investigation.
We contacted Shanghai Genechem Co., LTD. to consult the company staff. For our project, they thought that virus-mediated genetic modification will have some problems in practical application, because there are few therapies available in this way, preferring to use plasmids to directly transfect cells. So we hope to improve this area in the second year of the project. Moreover, Regarding price issues, the drug prices do not have much to do with actual costs. Finally, if we really want to market, they suggest that we can consider more issues related to safety, explore the effects of siRNA in more depth, and consult with relevant organizations.
3. the 7th Conference of China iGEMer Community – a start on the bioethical issues
Our team also participated in the 7th Conference of China iGEMer Community, where we presented our project and received some feedback. Some asked whether it was ethical to modify liver cells in the practical application. To solve this problem, we explored the ethical issues of our project in three ways.
First of all, we Interviewed Professor Yusheng Han of ethics in the Department of Philosophy, Nanjing University. He believes that ethics should not be a limiting factor to the development of science, but should progress together with science and technology, especially when it comes to the treatment of diseases, which is a technology for the benefit of mankind, and therefore there is no ethical problem in the design of our project.
Secondly, we set up a booth at the Hundred Clubs Battle held at Nanjing University to promote the project and ask students to answer the question "Would you accept the treatment of a disease by changing the genes of an organ?” The result is that the vast majority of people are receptive to gene editing as a form of treatment, but will be more concerned about safety.
