Gene therapy: Gene therapy was born with the development of modern medicine and molecular biology in the past 10 years, and has been widely used in clinical trials for the treatment of tumors and other diseases. As reported by Carroll in the United States, a new study has found that genetically engineered adenoviruses that can destroy head and neck cancer may be effective in treating ovarian cancer, pancreatic cancer, oral cancer and some lung cancers. Clinical trials using this virus, tentatively named 0NYX-015, confirmed their speculation. Researchers believe the virus can multiply in and destroy cancer cells. At the same time, the E1b gene of 0NYX-015 can disable the P53 gene, and only after the P53 gene is disabled can it replicate in this kind of cells. If the E1b gene is removed and the P53 gene comes into play, it will be impossible for the virus to replicate in normal cells, thereby protecting normal cells. Onashi from Japan reported that they analyzed the response of human gastric cancer cell lines MKN1, MKN7, MKN28, MKN45 and TMK-1 to recombinant adenovirus (AdCA P53) encoded by the wild-type P53 gene in vitro and found that two types of P53-specific growth inhibition was observed in vitro, and flow cytometry analysis and detection of DNA fragments indicated that the possible mechanism by which AdCA P53 causes gastric cancer cell death is apoptosis. In vitro studies have also shown that direct injection of AdcAP53 can significantly inhibit the growth of subcutaneously implanted tumors in P53 gene mutant MKN1 cell lines.

Relevant domestic research is similar to this. For example, the "Study on the Treatment of Non-Small Cell Lung Cancer with Tumor Suppressor Genes P16 and P53" conducted by a domestic medical school research center in recent years found that the combined application of these two tumor suppressor genes , can significantly improve the effect of inhibiting the growth of non-small cell lung cancer cells. They inoculated human non-small cell lung cancer cells subcutaneously into the backs of nude mice to establish a xenograft nude mouse lung cancer model. They used tumor suppressor genes P53 and P16 to be directly injected into the tumor and a combination of the two genes. The results showed that transfection of P53 and P16 genes alone or *** transfection of these two tumor suppressor genes can significantly inhibit the growth of tumor volume. Among them, the P16 gene has a stronger inhibitory effect than P53, and the combined application of the two genes has the strongest effect. In another study, they found that the combination of P53 and cisplatin can cause large-scale apoptosis in lung cancer tumors. This can not only keep the tumor cells in a completely suppressed state, but also avoid the toxic and side effects caused by patients taking large doses of cisplatin. Professor Wu Mengchao of Shanghai Oriental Hepatobiliary Surgery Hospital and others used interleukin 12 (IL-12) to treat liver cancer. Gene therapy research has achieved impressive results. They conducted controlled experiments on rats, and the results showed that IL-12 significantly prolonged the survival time of rats. At the same time, a retroviral vector packaging cell line with a recombinant IL-12 gene was directly injected into the spleen, and its efficacy was similar to that of local injection of liver cancer. The efficacy is similar and safer. Studies have shown that when tumors occur, proteins controlled by multiple oncogenes appear in large quantities in the human body and form a specific shape, thereby triggering the body to become cancerous. The special shape of these cancer-causing proteins is formed with the help of a molecule called Hsp90 (also known as a molecular chaperone). Huang Changzhi, associate researcher at the Institute of Oncology, Chinese Academy of Medical Sciences, and others designed a drug called Zao HA90 that specifically targets the effects of Hsp90. It can hinder the use of Hsp90, causing more than 5 kinds of oncogenes to lose their carcinogenic effects, and has a significant inhibitory effect on lung cancer cells, cervical cancer cells and breast cancer cells. Animal experiments show that the growth inhibition rate of solid tumors is more than 50%. , and has the characteristics of wide application range, small side effects, safety, intravenous injection, and easy use. It is the first new drug launched at home and abroad that can inhibit multiple oncogenes. In the gene therapy of cancer, positive lipids Body-mediated gene transfection has been the most extensively studied. Yoshihisa et al. intraperitoneally injected β-galactosoplasmase-positive liposome complex into nude mice bearing PC-1, and measured the transfection activity on the 3rd day and found that The expression of β-galactosidase in tumor tissue is higher than that in normal tissue. Human ovarian cancer suspension can form ascites cancer when injected into mice. Intraperitoneal injection of liposome-NApUC19 complex was used for treatment. The experimental results showed that mice receiving liposome-NApUC19 complex did not develop ascites cancer, but developed solid tumors, and their survival time was significantly longer than that of the blank group. Obstacles facing gene therapy include low transgene efficiency and lack of effective therapeutic genes. It is unrealistic to expect too high and be demanding at this stage. We can only focus on carrier research, focus on basic research, and identify guidance, efficiency and controllability as the ultimate goal.

The research on the molecular level of tumors in my country is close to the level of similar research abroad. The preparation of genetically engineered single-chain antibodies against human bladder cancer provides an effective new antibody for the biological treatment of bladder cancer.

Professor Chen Zhinan of the Fourth Military Medical University collaborated with Dr. Yang Zhi of a pharmaceutical company to discover a new functional gene for liver cancer and confirmed that it has the function of controlling the spread and metastasis of liver cancer. This gene was named "HAb18G". They prepared an anti-liver cancer antibody (HAb18) with high affinity and specificity to liver cancer cells, and used it as a carrier. They successively found in experimental diagnostic studies of liver cancer that this antibody can reduce lesions with a diameter of 0.5 cm. Cancer cells are killed, while normal tissue cells are not damaged.

Research by Lv Guiquan, chief physician of Zhejiang Cancer Hospital, and others has shown that P53 and P16 gene mutations are common molecular genetic events in the occurrence and development of esophageal cancer, and are related to esophageal cancer metastasis and patient survival. They used modern advanced molecular biology techniques (immunohistochemistry, PCR-SS-CP, PCR-FLP, ID-PCR, etc.) to detect protein expression, gene mutations, and heterogeneity of the P53 and P16 genes. Projects such as zygosity loss and P16 gene deletion. The results show that P53 and P16 gene mutations are one of the common genetic events in the occurrence and development of esophageal cancer. Because wild-type P53 is a tumor suppressor gene, it can induce programmed death of tumor cells, that is, apoptosis. It can specifically bind to NA sequences and reduce the resistance of tumor cells to programmed death by inhibiting or activating the transcription of other genes. A mutation that induces resistance to stimulation and loses normal function. The defective P53 gene, on the contrary, can inhibit the programmed death of tumor cells.

Doctors such as Zhai Xiaobo from Shanghai Sixth People's Hospital used the MTT method to measure the inhibition rate of 17 anti-cancer drugs on 86 cases of malignant tumors, and used polymerase chain reaction to observe the status of genes. The results showed that after statistically comparing the inhibition rates of anticancer drugs in the P53 gene normal group and the P53 gene abnormal group, it was found that the inhibition rate of most anticancer drugs in the former was significantly greater than the latter, thus concluding that when the P53 gene is mutated or deleted, When normal functions are lost, the tolerance of cancer cells to programmed death induced by anticancer drugs can be increased, thereby reducing the efficacy of anticancer drugs, that is, the resistance to anticancer drugs is significantly increased. Similarly, they used the same method to measure the inhibition rate of 17 anti-cancer drugs on 84 cases of malignant tumors. They also used multiplex polymerase chain reaction (PCR) to detect the deletion of 17 genes among them, and compared the results statistically. The results showed that similar to the status of the P53 gene, the inhibition rate of most anticancer drugs in the group with normal P16 gene was greater than that in the group with P16 gene deletion, further confirming the relationship between them.