According to the mechanism of action of anti-tumor drugs currently used in clinic, it can be roughly divided into

There are four categories: drugs that directly act on DNA and destroy its structure and function; Interfere with DNA synthesis

Drugs; Anti-mitotic drugs; Drugs based on tumor biological mechanism.

1. 1 drugs that directly act on DNA

1. 1. 1 alkylating agent

Action mechanism. From the perspective of organic chemistry, the reaction between alkylating agent and DNA is real.

This substance is a nucleophilic substitution reaction. There are good leaving groups on alkylating agents, which can form insufficient motivation in the body.

Active intermediates or other compounds with active electrophilic groups, DNA contains

Electron-rich groups (such as amino, sulfhydryl, hydroxyl, carboxyl, phosphate, etc.). ) is reacting with DNA.

The alkylating agent reacts with DNA by generating carbocation or directly.

And DNA are alkylated in the form of SN 1, thus affecting or destroying the structure and work of DNA.

Yes, DNA can't play a role in cell proliferation.

1. 1.2 metal platinum complex

Action mechanism. Cisplatin complex is hydrolyzed into hydrate after entering tumor cells, hydrate

In vivo, it forms a closed five-membered chelate with two guanine bases N7 of DNA.

Ring, thus destroying the hydrogen bond between purine group and cytosine on two polynucleotide chains, disturbing

The normal double helix structure of DNA is disordered, which makes it locally denatured and inactivated and loses its replication ability. counter

The platinum complex of formula has no such effect.

1. 1.3 bleomycin

Action mechanism. Bleomycin antitumor drugs are naturally occurring glycopeptides.

Tumor antibiotics directly act on the DNA of tumor cells, destroying and breaking DNA chains, most of which

Eventually lead to the death of tumor cells.

1.2 drugs that interfere with DNA synthesis

The action mechanism of 1.2. 1

Drugs that interfere with DNA synthesis, also known as anti-metabolic and anti-tumor drugs, inhibit DNA.

Metabolic pathways of folic acid, purine, pyrimidine and pyrimidine nucleoside are synthesized, thus inhibiting tumor size.

The survival and replication of cells lead to the death of tumor cells.

1.2.2 drug classification

Folic acid antagonists, pyrimidine antagonists, purine antagonists

1.3 antimitotic drugs

Mechanism of action:

Drugs interfere with mitotic phase (M phase) of cell cycle and inhibit cell division and proliferation.

Breeding. In the metaphase of mitosis, the spindle is formed, and the replicated chromosomes are arranged into

On the equatorial plate in the middle, to the late mitosis, these two groups of chromosomes rely on the micro in the spindle.

The interaction between the tube and motor protein moves to the centrosome of the two poles. The role of antimitotic drugs

Microtubules in cells prevent chromosomes from moving to bipolar centrosomes and inhibit tumors.

Cell division and proliferation [3].

Mitotic inhibitors have strong affinity with tubulin, and most of these inhibitors

It is a natural product and derivative extracted from higher plants.

2. New anti-tumor drugs

Traditional anti-tumor drugs play a role by affecting DNA synthesis and cell mitosis.

Yes, these tumor drugs are very effective, but they lack selectivity and have great side effects.

It's huge. People hope to improve the targeting of anti-tumor drugs and attack tumor cells with high selectivity.

Without harming normal tissues.

With the development of life science, the biological mechanism of tumor occurrence and development is gradually recognized by people.

People gradually realize that the research of anti-tumor drugs has begun to move towards targeted and rational drug design.

Through research, some highly selective new drugs have been produced.

Drug classification and mechanism of action:

Targeted drugs. From the perspective of targeted therapy of anti-tumor drugs, it can be divided into three layers.

Time:

The first level: drugs are directed to the site where tumors occur, such as clinical use.

Interventional therapy is targeted therapy at organ level, also known as passive targeted therapy.

The second level: using the biological characteristics of tumor cell uptake or metabolism, drugs will be

The target is located on the tumor cells to be killed, that is, cell targeting, which has the nature of active orientation.

For example, monoclonal antibodies (monoclonal antibodies [4]) and toxins and nuclides can be prepared by using the differences in antigen properties of tumor cells.

Or conjugates of anticancer substances, directionally accumulate on tumor cells and kill them, with good effect [6].

The third level: molecular targeting, using molecular biology between tumor cells and normal cells.

Differences in genes, enzymes, signal transduction, cell cycle, cell fusion, swallowing and metabolism.

According to different characteristics, anticancer drugs will be located on the target cells of biological macromolecules or small molecules and play an inhibitory role.

Inhibit the growth and proliferation of tumor cells and eventually make them die.

Development of vascular inhibitor drugs. Tumor growth must have sufficient blood supply.

In the process of development and metastasis, the growth of new blood vessels is a necessary condition [3]. New angiogenesis is involved

It is transformed into many links, such as the degradation of vascular endothelial basement membrane and the increase of metalloprotease activity.

There are many growth regulators in the proliferation of vascular endothelial cells, the reconstruction of new blood vessels and the formation of new basement membrane

Including fiber growth factor (FGF) and vascular endothelial growth factor.

(VEGF), platelet-derived growth factor (PDGF), angiopoietin and their transformation.

Growth factor (TGF). They can promote the formation of new blood vessels and increase DNA synthesis. otherwise

Some regulatory factors can inhibit the growth of vascular endothelium, such as angiostatin, endostatin and interferon.

Interferon α and γ, etc. In view of the above different links and related objectives, a variety of.

Angiogenesis inhibitors, such as Marimastat, have inhibitory effects on metalloproteinases and inhibit blood.

Endostatin is a kind of endostatin that grows in the endothelium of the tube, and it is a vitamin A antibody that inhibits the recognition of integrins.

And a nonspecific inhibitor thalidomide. Dozens of such new drugs have entered clinical trials.

Has therapeutic effect on various tumors and tumor metastasis, and can be combined with common anticancer drugs.

Improve the curative effect, but its exact curative effect still needs clinical verification.

3. Development prospect of anti-tumor drugs

3. 1 Targeted antitumor drugs will continue to develop.

3.2MDR (multidrug resistance) reversal agent

MDR (drug resistance) is the most important reason for the failure of tumor chemotherapy, and it is also the reason for the failure of tumor chemotherapy.

A major difficulty, so it is very necessary to find and develop MDR (multidrug resistance) reversal agents, or

Adding two or more anti-tumor targeted drugs may further improve the traditional cytotoxicity.

Anti-tumor effect of chemotherapy regimen [4].

3.3 Anti-tumor metastasis drugs

More than 50% of clinically diagnosed tumor patients have metastasized, and most of them.

All cancer patients eventually died of metastasis, so anti-tumor metastasis drugs, such as tumor metastasis, were developed.

Polypeptide migration inhibitors and tumor cell hydrolase inhibitors are also necessary. Lv Yanen and others passed.

The antitumor effect of cytotoxic T lymphocytes modified by IL-2 gene was studied, and the following conclusions were obtained.

Conclusion: CTL transfected with IL-2 gene can directly kill and induce specific activation.

Sexual anti-tumor immune response can significantly enhance the anti-tumor effect in vivo and effectively inhibit experimental lung.

Growth of metastatic tumor [5].

3.4 Gene therapy

On June 5 5- 10/October 7, 2002, the discovery project awarded by the Nobel Prize in Physiology and Medicine was "Cell".

Programmed death is controlled by genes. This discovery makes people realize that with the introduction of genes

In-depth study of the system, controllability of gene expression and development of better and more therapeutic genes.

Now, people can introduce wild-type tumor suppressor genes, suicide genes, drug resistance genes and antisense genes.

Oligonucleotides, tumor genetic engineering tumor bacteria, etc. Treat cancer [3]. Gene therapy will become comprehensive.

A very effective method to treat malignant tumor.

summary

Although traditional anti-tumor drugs have strong effects, their specificity is poor and their side effects are great.

Therefore, its proportion in the future anti-tumor drug market will decrease day by day; the same

At present, anti-tumor drugs with targeted function will occupy the market for a long time to come.

A large share; Gene therapy needs further research.