Malaria parasite cure cancer? Is it a lifesaver or Pandora's box

"The use of malaria parasites to successfully treat patients with advanced cancer" - Chen Xiaoping, a professor at the Guangzhou Institute of Biomedicine and Health of the Chinese Academy of Sciences, exploded on social media such as circle of friends and Weibo in a public speech at the SELF Forum of the Chinese Academy of Sciences.

Chen Xiaoping said that the team found that tumor mortality and malaria incidence showed a negative correlation, malaria parasite is helpful in the treatment of cancer, the current clinical trial found that 10 patients, 5 people have obvious treatment effect, of which 2 may be cured.

After the continuous fermentation of social media and self-media dissemination, this statement, which has not yet been officially published in academic journals in the form of papers, has been exaggerated and even misread, and even regarded as the last glimmer of hope for patients with advanced cancer.

However, many clinicians and scholars have come out to debunk the rumors and question this research that does not yet have accurate statistics and large sample size clinical trial verification.

So, is the "malaria parasite cure cancer" a life-saving straw or a Pandora's box? The surging news (www.thepaper.cn) reporter interviewed a number of experts to interpret.

Malaria parasite cancer treatment mechanism ≠ immunotherapy

Can cancer be treated by injecting a shot of blood containing the parasite and controlling the density of the parasite with artemisinin? At first glance, this sounds quite a bit of a "dead horse as a live horse doctor" - to attack poison with poison. It should be clear that unlike the method of Chinese medicine using centipedes, whole scorpions, dew hives, geckos, etc., malaria parasite cancer treatment is not to attack the "poison" of cancer cells with the "poison" of malaria parasites, but to try to stimulate specific immunity against cancer through malaria parasites.

Before the advent of immunotherapy, cancer most commonly used surgical removal of tumors, chemoradiation to eliminate tumors, and anti-cancer drugs to combat cancer cells. Cancer immunotherapy, on the other hand, destroys cancer cells through the body's own immune system. American immunologist James P. Allison and Japanese immunologist Tasuku Honjo also received the 2018 Nobel Prize in Physiology or Medicine for their contributions to immune checkpoint therapy.

Conventional cancer treatment methods are aimed at malignant tumor cells, while immunotherapy is mainly aimed at immune cells, by inhibiting immune negative regulators, activating the immune system, enhancing the recognition and killing of tumors by immune cells, so as to achieve tumor clearance. Compared with the current traditional treatment methods, immunotherapy has the advantages of good efficacy and long duration, and is one of the most anticipated treatment methods at present.

However, the mechanism of malaria parasite cancer treatment is different from immunotherapy. Ruan Yuanyuan, a professor in the field of biology at fudan university's basic medical school, said in an interview with the surging news reporter: "Strictly speaking, malaria parasite cancer treatment cannot be called immunotherapy, but its anti-cancer principle is related to human immunity. The immunotherapy drugs that have been put into use on the market now have confirmed targets, while the targets of malaria parasite cancer treatment are unclear. According to clinical data, the current effective rate of immunotherapy is not more than 30%, but it is the last method of tumor treatment at present. ”

Individual trials ≠ valid samples

During his early years of study, Professor Chen Xiaoping stumbled upon a geographical distribution map of malaria incidence and cancer mortality worldwide, which seemed to have a negative correlation, so he had the initial idea that "malaria may be able to cure cancer"; subsequently, their team found in a mouse model that malaria-causing malaria parasites can significantly inhibit tumor growth, and also studied the mechanism behind it, possibly by activating the immune system function of mice; in the past two years, Their team began clinical trials using malaria parasites for advanced cancer at several hospitals. Of the ten patient data made public in the speech, five "had an effect" and two "seemed to have been cured."

So, what is the process from "whimsical" to the final production and listing of the finished drug? According to Ruan Yuanyuan, a professor in the field of biology at Fudan University's School of Basic Medical Sciences, the development of a new drug usually consists of three stages

, which takes a long time:

First of all, basic medical experiments need to be done with tumor treatment. 1. It is necessary to study the occurrence of different types of tumors and the causes of metastasis and drug resistance, and intervene in their causes, so as to explore the targets of therapeutic drugs and the possibility of their drug formulation;

2. Study the feasibility of effective targets that can be drugged, design drug types, and select more effective programs from them.

Second, preclinical studies should be conducted on drugs. 1. Use animal models to test the safety and efficacy of the drug; 2. Quality control of the production process of the drug to ensure the stability of each batch of drugs; 3. Pharmacokinetics research, including the absorption, distribution, biochemical metabolism and excretion of the drug in the body, especially the law of blood drug concentration changes with time.

Finally, enter the clinical study, that is, conduct drug experiments on humans. Phase I clinical trials: subjects are 20-30 healthy volunteers (except for certain specific drugs such as anti-tumor drugs, anti-AIDS drugs, etc.), study the efficacy and pharmacokinetics of drugs acting on the human body, explore safe and effective doses, and observe drug side effects;

Phase II clinical trial: subjects are 100 target patients, preliminary evaluation of the efficacy and safety of drugs for these patients, study the impact of the occurrence and development of the disease on the efficacy of drugs; Phase III clinical trials: the minimum number of cases tested is 300 cases, to further verify the efficacy and safety of drugs for patients with target indications, the samples in this phase of the trial in addition to the number of more than the previous two stages, the geographical distribution of samples is also wider.

However, the traditional drug production process does not seem to be suitable for the study of malaria parasite cancer treatment. "Malaria parasites themselves cause malaria, and although the use of artemisinin can control infection and fever in the short term, its side effects cannot be fully controlled, and its safety itself is a paradox." The successful development of a new drug can be described as a long road, there was once a drug for the treatment of AIDS has passed the first two phases of clinical trials, but phase III did not pass, the research and development process took ten years, billions of dollars hit the water. There is no sufficient clinical data to support the effectiveness of malaria parasite cancer treatment, individual cases cannot be generalized, and individual trials may not be effective samples. Ruan Yuanyuan said.

Can high risk lead to high rewards?

As a parasite, it is unknown whether the situation of the parasite after entering the human body is completely controllable. Compared with ordinary people, most cancer patients, especially those in advanced stages, have cachexia. Cancer cachexia is a complex syndrome that often occurs in tumor patients, the main clinical manifestations are weight loss, loss of appetite, anorexia, muscle atrophy, anemia, edema, etc., these symptoms may be related to the rapid consumption of the tumor itself, but also related to the patient's long-term bed rest after cancer, no exercise, no appetite to eat malnutrition.

Nearly 80% of patients with gastrointestinal tumors will develop cachexia in the advanced stages of tumors. So, will the parasite, as a parasite, enter these patients' bodies, make their physical condition worse?

Infection with the malaria parasite itself has the risk of malaria, Lu Yuxia, deputy director of the Infection Department and gastroenterologist of Tongji Hospital affiliated to Tongji University, told the surging news reporter, "Malaria is a parasitic infectious disease with a high fatality rate, which is caused by infection with malaria parasites." Human malaria is caused by four different species of Plasmodium vivax, Plasmodium vivax, Plasmodium ovate, Plasmodium trichophyllum and Plasmodium falciparum. The most severe clinical type is caused by Plasmodium falciparum; the main clinical manifestations include chills, high fever, profuse sweating, severe headache, general aches, fatigue, and varying degrees of impaired consciousness. Other symptoms associated with organ failure may occur, such as acute renal failure, pulmonary edema, circulatory failure, central failure, and even death. Today's tumor treatment pays more attention to precision therapy (targeted therapy) to reduce the damage to normal cells, but the parasite parasite entering the body is unpredictable, and the autoimmunity of cancer patients is weaker than normal people, and it is also necessary to be vigilant against the public safety problems caused by this, so we must be cautious. ”

Any new drug is developed to improve efficacy and reduce risk. But is the high-risk approach to cancer treatment by plasmodium really rewarding? At present, there have been no large-scale clinical trials to prove that malaria parasites can cure cancer, and 10 randomized patients cannot form effective conclusions. To verify the effectiveness of a therapy in medicine, there is an important indicator, that is, to observe for 5 years to see if the cancer has recurred. In the current study, the earliest patients were observed for only about 2 years.

Ruan Yuanyuan, a professor in the field of biology at the Basic Medical College of Fudan University, said that the limitation of malaria parasite cancer treatment is that there is no horizontal comparison, "For cancer patients, doctors will choose the best solution to reduce the harm to the patient's body." So, compared with the drugs already put into use on the market, whose safety and efficacy are stable, what is the advantage of malaria parasite cancer treatment, which can cause an excessively strong inflammatory response in the human body? With the option of other more reliable, safe and effective tumor immune drugs, why should patients take the risk of trying malaria parasite therapy with unknown efficacy but great side effects? ”

Nguyen Yuanyuan suggested that it would be more feasible to extract active ingredients, such as certain proteins or small molecules, from the malaria parasite than to directly inject blood containing the malaria parasite into the patient's body.

Where are the ethical boundaries of medical experimentation?

The Declaration of Helsinki, drafted by the World Medical Association, a statement of ethical guidelines for the conduct of human medical research (including the study of the human body itself or related data) by physicians and others, clearly states: "The ethical standards to which medical research must be observed are: to promote and ensure respect for human subjects and to protect their health and rights; although the primary purpose of medical research is to acquire new knowledge, this purpose should never take precedence over the rights and interests of individual research subjects; in medical research, Physicians are responsible for protecting the life, health, dignity, integrity, right to self-determination, privacy, and confidentiality of the personal information of the subjects of the study. The responsibility for protecting study subjects must always be on the doctor or other health care professional and never on the study subjects, even if they give their consent. ”

So, has the injection of red blood cells containing malaria parasites into patients been approved by the ethics committee? According to the website of the China Clinical Trials Registration Center, corresponding to the three hospitals involved in the research on the treatment of malaria parasite cancer, a total of three studies related to the use of malaria parasites for cancer immunotherapy have been registered, which have passed the approval of the Ethics Committee of China Registered Clinical Trials, the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University and the Ethics Committee of Yunnan Kungang Hospital.

However, Wang Liming, a professor at the Institute of Life Sciences of Zhejiang University, wrote an article questioning: "The conditions for Chen Xiaoping's team to recruit patients in clinical research are not at all the ineffectiveness of any other methods that Chen Xiaoping said, and there is no way out!" Even, in a clinical study they began in 2017, there was this one (the information came from the database of the China Clinical Trials Registry): 'Patients who have not previously received anti-tumor therapy such as surgery/radiation therapy/chemotherapy/targeted drugs, and who refuse to accept the above treatments and strongly request admission, need to meet all the remaining requirements of the inclusion criteria.' That is to say, even if a patient has just fallen ill, no formal treatment (including surgery and chemotherapy) has been performed, and as long as he is 'strongly requested', a malaria parasite test can be carried out! (An interesting contrast is that the same team submitted the English clinical trial notes in www.clinicaltrials.gov, but there was no 'strong demand' entry.) This condition leaves little room for inducing more patients to join clinical trials — even those who have just discovered the disease and should have undergone a variety of formal treatment options. I'm curious, how many of the patients currently being treated with malaria parasites are in this situation? How many of them, if regular treatment had started early, could the cancer have really been cured or apparently under control? How many of them may have been delayed by malaria parasite therapy?

The public's awareness of science popularization needs to be improved urgently

According to data released by the World Health Organization (WHO), it is expected that by 2020, the number of new cancer cases will reach 15 million per year. Many lawbreakers are taking advantage of people's fear of cancer to pit patients for huge profits. Whether it is the Wei Zexi incident or the Quanjian pyramid scheme, it reflects the weak awareness of popular science from the side. For cancer patients, we cannot listen to and believe in some self-media for the eyeball-catching "title party" poisonous chicken soup, let alone rush to the hospital superstitious health care product marketing gimmicks, but to receive formal treatment in regular hospitals.

Huang Hua, assistant director and chief physician of the Department of Gastrointestinal Surgery of fudan university affiliated cancer hospital, said: "Ordinary people should adopt a rational attitude towards scientific experiments, and in the absence of accurate statistical data and large sample size clinical trial verification, they cannot blindly pursue, of course, can not completely deny." At present, the most effective treatment for solid tumors is still a combination of surgery-based therapy, combined with radiotherapy and chemotherapy, immunotherapy and drug therapy. ”

Dr. Zhao Yue, who is currently engaged in digestive system tumor research at the University of Cologne in Germany, and the surging news reporter "In order to let the public increase the common sense of science and understand medical research, some hospitals and research centers in Germany have open days for the public to visit, understand some daily research projects, and also specially design some simple and very interesting small experiments, so that the public, including children, understand some simple scientific experimental principles." The University of Cologne's Comprehensive Oncology Centre (CIO) also runs short-term training courses for high school students every summer, encouraging and attracting young students interested in life sciences medical research and clinical practice to improve their contact and understanding of some oncology-related topics, and to impart and help them learn more about medical research. ”

Only when the people's scientific knowledge increases and scientific literacy can they not be confused and blinded by the information bombardment of the self-media era.