2021 SOHO Expert Interview｜Professor Jing Hongmei talks about the progress and prospects of MCL treatment

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodg lymphoma.
Its occurrence and development may be related to cell cycle disorders.
The prognosis of patients is poor and the recurrence rate is high
.

The team of Professor Jing Hongmei from Peking University Third Hospital conducted a study to explore the role of cell division cyclin 20 (CDC20) in MCL.
The study was selected for the poster presentation of this year's SOHO conference
.

Yimaitong specially invited Professor Jing Hongmei and the first author of the study, Dr.
Yingtong Chen, to interview and talk about the significance of this study and the prospects of MCL treatment
.

Yimaitong: MCL is a relatively rare type of B-cell lymphoma.
Could you please introduce the current status of MCL treatment in my country? Professor Jing Hongmei's MCL is relatively rare, accounting for about 7% of lymphomas.
It has both the aggressiveness of aggressive lymphoma and the incurable characteristics of indolent lymphoma
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According to the statistics of MCL patients in 19 centers in China, there is a certain difference between the age of onset of MCL patients in China and foreign MCL patients.
At present, the statistical analysis includes more than 600 MCL patients, and the median age of the patients is 59 years old
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The median age of foreign MCL patients is 68 years old, and patients over 65 years old account for 2/3
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It can be seen that the age of onset of MCL patients in China is relatively young, and most patients can tolerate high-dose chemotherapy
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Therefore, the treatment options for MCL patients in China and foreign MCL patients are not the same.
A real-world study in the United States at this year’s EHA meeting that included more than 4,000 patients showed that the BR regimen (bendamustine, rituximab) Monoclonal antibody) is a very important treatment option for MCL patients in the United States
.

The first-line treatment of MCL patients in China is mainly based on the age of the patient.
For patients younger than 65 years old, if the general condition is good and can tolerate high-dose chemotherapy, the first choice is a chemotherapy regimen containing high-dose cytarabine, and then combined with autologous hematopoietic stem cells Transplantation can improve the depth of remission and prolong the survival period of the patient
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For patients over 65 years of age, if they cannot tolerate high-dose chemotherapy, R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or BR regimen can be selected
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With the emergence of some new small molecule targeted drugs, some experts suggest that small molecule targeted drugs should be applied to the first-line treatment of MCL in order to further improve the depth of remission of patients and delay recurrence.
However, this recommendation requires more Research support
.

Yimaitong: The research conducted by you and your team explored the role of CDC20 in the occurrence of MCL, and published the research results at this year's SOHO conference.
What is the background and purpose of this research? Dr.
Yingtong Chen CDC20 is a key molecule in the cell cycle checkpoint, which regulates the cell cycle process by activating the advanced cell division promotion complex (APC)
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It has been reported that CDC20 is highly expressed in a variety of tumors and exerts a carcinogenic effect, and its expression level is closely related to the clinical pathology and prognosis of patients
.

In our previous research, through sequencing analysis, bioinformatics analysis, and molecular biology research, we found that CDC20 is highly expressed in MCL, and MCL is also a cell cycle disorder disease, so we focus on cell cycle-related molecules, The purpose is to explore the influence of CDC20 on the occurrence and progression of MCL, and whether CDC20 can be used to treat MCL
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Yimaitong: Could you please interpret the results and significance of this study in detail? Can the results of this research be translated into clinical research in the future? In this study, Dr.
Yingtong Chen found that the CDC20 molecule was highly expressed in the five cell lines of MCL through qPCR analysis, and then analyzed 127 patients in the database through bioinformatics research and found that the CDC20 molecule was highly expressed The prognosis of patients is worse, so we initially judged that CDC20 may play a role in the occurrence and development of MCL
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In the following molecular biology experiments, we found that CDC20 has corresponding effects on the growth, proliferation, migration, invasion and other aspects of MCL cell lines.
After treating MCL cell lines with CDC20 inhibitors, we found that CDC20 inhibitors can inhibit cells.
The proliferation of cells promotes cell apoptosis, while also inhibiting cell migration and invasion
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We also established a tumor-bearing mouse model by injecting MCL cell lines into nude mice and conducted in vivo experiments.
After intraperitoneal injection of CDC20 inhibitors into mice, the tumors were significantly reduced
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In view of the above research results, we preliminarily judge that CDC20 can be used as a new therapeutic target for MCL, but the transformation from molecular biology research to clinical research still needs more exploration, so a lot of basic research is needed in the future for verification, and we also The research and exploration of the combined application of new drugs and CDC20 inhibitors will be carried out, and we look forward to the emergence of more effective exploration programs
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Yimaitong: In recent years, what new research directions are there in the treatment of MCL? The pain and difficulty in the treatment of MCL by Professor Jing Hongmei is the recurrence of the disease.
About 80%-90% of patients will relapse.
After recurrence, most of the disease progresses rapidly and the prognosis is poor.
The survival time of relapsed patients is only about 1 year
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Therefore, there is an urgent need for new drugs to improve the prognosis of MCL patients
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At present, there are more and more researches and explorations on MCL small molecule targeted drugs, such as BTK inhibitors, PI3K inhibitors, and BCL-2 inhibitors.
CAR-T cell therapy also shows a good therapeutic prospect in MCL
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Our center also has a number of ongoing clinical trials for MCL, such as the study of a new generation of BTK inhibitor LOXO-305 for the treatment of MCL.
At the same time, two CAR-T cell therapy studies are in preparation.
We look forward to the future results of these studies.
Provide new treatment options for MCL patients
.

Professor Jing Hongmei, Director, Chief Physician, and Doctoral Supervisor, Department of Hematology, Peking University Third Hospital, Vice Chairman, Oncology Expert Committee, Chinese Women Physicians Association, Vice Chairman, Lymphoma Special Committee, Chinese Medical Education Association, Youth Committee, Blood Branch, China Medical Education Association Vice Chairman of the Association Member of the Standing Committee of the Geriatric Oncology Committee of the Chinese Society of Geriatrics Published more than 60 papers and participated in the compilation and translation of 5 books.
Dr.
Chen Yingtong, Peking University Third Hospital, PhD student in internal medicine (hematology).
Instructor: Professor Jing Hongmei.
Research direction: Research on the pathogenesis of lymphoma.
Published SCI during his Ph.
D.
3 papers, 5 postal exchanges at home and abroad, "read the original text", we make progress together