Team:Nanjing NFLS/Background

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• Home
• Project
  • Description
  • Background
  • Design
  • Experiment
  • Demonstrate
  • Notebook
  • Vision
• Parts
• Safety
• Model
• Team
  • Team Members
  • Attributions
  • Collaborations
• Human Practices
  • Overview
  • Integrated Human Practices
  • Public Engagement
• Judging

Background

• Current liver cancer treatments
  • Surgery
  • TACE treatment
  • Local ablation therapy
  • Chemotherapy
• Neoantigen
• References

Current liver cancer treatments

Surgery

A method of surgically removing all or part of a tumor. Surgical resection is one of the most effective and important treatments in cancer therapeutic. However, hepatectomy is difficult due to the complex anatomy of the liver and abundant blood supply. Although hepatectomy is currently the preferred treatment for most liver cancers, the 5-year recurrence rate after surgery is 40% to 70%. Moreover, many patients are unable to undergo surgery because of their physical and medical conditions. ^[1]

TACE treatment

TACE (transcatheter arterial chemoembolization) is one of the commonly used treatments for liver cancer. For patients with liver cancer who are unable to undergo surgical resection, TACE treatment can significantly delay tumor progression and even achieve partial remission. However, some problems cannot be ignored in TACE treatment, including the inability to eliminate residual cancer, may stimulate the proliferation of residual cancer cells and vascular endothelial cells, and may activate hepatitis virus replication. These problems have limited the application of TACE and increased the number of patients. Most problems cannot be solved by improving the method of TACE. ^[1]

Local ablation therapy

Local ablation therapy is a treatment method for inducing tumor necrosis and killing tumor tissue by changing the physical environment (via RF, microwave, laser, freezing, etc.) or injecting chemicals (anhydrous ethanol, etc.) in the tumor. However, the specificity of local ablation treatment is not high, which will bring complications including pain, fever, pleural effusion, and bleeding. ^{[1] [2]}

Chemotherapy

Chemotherapy is therapy killing liver cancer cells through drugs. It is a systemic treatment for the treatment of primary, metastatic and subclinical metastases. Usually, the drug is administered intravenously or orally. Chemotherapy drugs for liver cancer include vinblastine, doxorubicin, mitomycin, cisplatin, etc., but traditional chemotherapy drugs are not effective in the treatment of liver cancer and the side effects are large. Target drug therapy is a new breakthrough in the treatment of hepatocellular carcinoma in recent years and is also an indispensable part of the comprehensive treatment of liver cancer. Target therapy can specifically act on the key molecules in the growth process of hepatoma cells, thereby killing tumor cells, while protecting the normal cells to the greatest extent. Sorafenib and sunitinib are the most commonly used target drugs for the treatment of liver cancer, but these two molecularly targeted drugs also have problems. First, the efficiency is low, only a few patients are effective after taking it; secondly, it is easy to produce drug resistance. The disease will progress again after taking for a period of time. Since the liver plays an important role in the human body and bears many functions and liver cancer develops rapidly, there are many limitations in the development of target drugs.

 

Neoantigen

Cancer cells have characteristics of genetic instabilities and accumulate somatic mutations rapidly. The genome sequencing of cancer cells revealed heterogeneity, and tens of thousands of somatic mutations amassed in individual patients. There are various types of mutations, such as point mutations, insertion/deletions, gene amplification, and translocations in cancer cells. Some of them may lead to nonsynonymous somatic mutations altering the amino acid coding sequences and creating uncontrollable and abnormal proteins to promote cell proliferation. These aberrant peptide sequences could be seen by our immune system, so these peptides form a tumor-specific antigen called neoantigen. Neoantigens could be presented by the major histocompatibility complex (MHC; also known as human leukocyte antigen (HLA) in humans) on the cell surface and recognized by the T lymphocytes. As neoantigens are tumor-specific and not expressed by normal cells, they are ideal therapeutic targets wh have great potential to maximize the therapeutic specificity, overcome the immune tolerance, and minimize the risk of autoimmunity. A series of recent vaccine studies revealed that neoantigens are an ideal target for tumor immunotherapy.

Despite recent advances, many challenges remain in the development of neoantigen vaccines. Not all mutations can elicit a highly effective immune response, and the prediction and screening of nascent antigens remain the biggest challenge in the development of the neoantigen vaccine.

Therefore, we ask such a question: can we bypass the step of predicting and identifying the nascent antigen, but to directly allow the tumor to present a peptide with strong immunogenicity- a neoantigen？

References

[1] Advances in treatments for primary liver cancer. Journal of Abdominal Surgery, 2019 Jan. doi: 10.3969/j.issn.

[2]王桂琴,陈玉华.肝癌微波消融术后并发症分析及护理[J].中西医结合护理(中英文),2019,5(06):126-129