New advances in the study of the molecular mechanisms of tumor cells in recent years have led to the discovery and synthesis of many new antitumor drugs that have brought many new life opportunities to tumor therapy. These drugs can inhibit the survival of tumor cells by acting selectively at specific molecular sites, allowing tumor patients to recover. In this paper, we will only review the recent advances in this area in order to provide readers with a literature review. I. Basic Overview Despite the tireless efforts to improve the prognosis of tumors and find new means of curing them, the prognosis of the four most common and deadliest epithelial tumors in humans —— progressive lung cancer, intestinal cancer, prostate cancer and breast cancer is still not promising. Recent studies have shown that the process of damage to a large number of normally regulated genes of the organism as a result of the encroachment and metastasis of cancer cells is in essence a chronic disease process caused by the known carcinogenic effects on the biological organism. Xuebin Wu, Department of Hematology, Beijing Jitan Hospital, Capital Medical University The natural state of carcinogenesis and cancer development has suggested that such diseases can be controlled by blocking their biological processes. A new pathway to control such diseases with great potential is tumor chemoblocking. Chemoblockade can inhibit the development of aggressive cancers either by drugs or natural factors, either by blocking DNA damage —- which can induce the cancer process, or by reversing the biological effects of malignant precursor cells that have already undergone the process. Recent studies on the mechanisms of oncogenic action have led to the synthesis of certain new anticancer drugs that can inhibit tumor growth in experimental animal models by selectively activating specific molecular sites of action under experimental conditions. Such specific molecular sites of action are currently being investigated, such as retinoic acid receptors, cyclic hydrogenase and estrogen receptors. Experimental and epidemiological studies of carcinogenic effects have shown that more than 90% of cancers are associated with environmental factors, which is of great significance for identifying and standardizing the effects of chemical blocking agents. There are four possible transitions of precancerous cells: (1). Increased apoptosis; (2). Increase cell maturation and differentiation; (3). Decrease cell proliferation; and (4). Decrease vascular proliferation. Mutagenesis can damage cells and disrupt normal regulation, leading to apoptosis and lack of maturation of normal cells, thus allowing tumor cells to overproliferate. Therefore, another implication of chemoblocking studies is to find certain factors that can block these disruptions or inhibit mutagenesis. II. Molecular sites of retinoic acid receptors Retinoic acid receptors modulate their target gene expression through the corresponding interaction of homodimers or heterodimers with specific DNA response elements. Such nucleic acid receptors for retinoic acid are important molecular target sites for new chemo-blockers. There are six known retinoic acid receptors, namely retinoic acid receptors α, β, and γ (RAR-α, RAR-β, and RAR-γ) and retinoic acid X receptors α, β, and γ (RXR-α, RXR-β, and RXR-γ), which are conversion factors regulating specific genes with specific response elements. It can be believed that the new retinoid drugs now being synthesized are specific ligands for these receptors and that retinoids are necessary for the differentiation of certain cavernous organs such as the digestive tract and bronchial epithelium. deficiency of RAR-β is a hallmark of many lung cancers and many precancerous lesions of the oral epithelium and bronchial tract. Treatment with 13-cis-retinoic acid restores RAR-β expression, while reversing the progression of precancerous lesions. Recent studies on RXRs involving molecular loci have focused on the development of selective ligands for the three RXRs forming heterodimers that, like many other nucleic acid receptors including RARs, thyroid receptors, vitamin D receptors, and a large group of other nucleic acid receptors such as orphan receptors (orphans), still have unidentified ligands. Newer retinoic acid analogs can target specific retinoic acid receptors, e.g., 9 cis retinoic acid can be pegged to both RARs and RXRs; LDG-1069 specifically pegs to RXRs and LDG-1550 specifically pegs to RARs receptors. In addition, N-4 hydroxyphenyl vincristine (4-HPR) is a potential apoptosis inducer and also upregulates RAR-β expression. III. Molecular sites of cyclooxygenases Although many chemo-blockers have been developed in the past, recent advances in the molecular biology of carcinogenesis have made it possible to develop new and better drugs based on a broader mechanism. In terms of chemical blockers at the molecular site of action, the most exciting discovery is the overexpression of cyclooxygenase 2 (COX-2), a key enzyme in the formation of prostaglandins from arachidonic acid, which is an early and central marker of colonic carcinogenesis, providing an important target site for the development of such drugs. The mechanism by which COX-2 activation promotes tumor formation remains unclear, but its apoptosis-inhibiting effect is clear. Clinically, the next step is to develop drugs that selectively inhibit COX-2 without gastrointestinal side effects. It has been well documented that non-selective COX-inhibitors can block cancerous lesions in the colon under experimental conditions, and Sulindac has been used clinically to inhibit colon adenocarcinoma formation. However, such non-selective inhibitors cannot be widely used as a general-purpose chemo-blocker. The recent synthesis of safe and selective COX-2 enzyme inhibitors such as MF-tricyclic that inhibit polyp formation is a new development in human research on chemical blockade of colon cancer. Clinical studies with selective COX-2 inhibitors will be an important practical process to apply chemical blocking agents for effective control of human cancer. IV. Molecular loci in breast and prostate cancer While estrogen has long been recognized as a promoter of carcinogenesis in the breast, its receptor antagonism is of great experimental and clinical importance for the prevention and treatment of breast cancer, and work needs to be done on how to suppress breast estrogen levels without losing its beneficial antagonistic effects in bone, brain and cardiovascular tissues. The development of selective estrogen receptor models can help to achieve this goal, and central to this goal is the development of a new drug that is designed to act as an estrogen antagonist in tissues such as the breast, uterus, and ovaries where estrogen exerts its effects and promotes cancerous lesions. Tamoxifen, a potent estrogen receptor antagonist, has been shown to block primary breast cancer through molecular, cellular and animal studies. A phase III randomized study was initiated in 1992 under the Women’s Health Study, and has been completed in 14,000 women. Results are expected to be released later in 1999. Although Tamoxifen has been shown to have an inhibitory effect on breast carcinogenesis in animals and women, it is not effective in the uterus and may increase the chance of endometrial cancer. Therefore, it is most intriguing to offer a new selective estrogen receptor model (SERM), arm e.g., a drug similar to Raloxifen, which has a potential chemoblocking effect on breast cancer without the risk of increased uterine lesions. In animal studies, Raloxifen was a potent breast cancer blocker but did not promote the proliferation of uterine epithelium. In fact, as an estrogenic agent, Raloxifen has been used clinically to combat osteoporosis and to maintain bone stability in menopausal women. However, to date, there is insufficient information to demonstrate that Raloxifen has a clinically useful role in blocking breast cancer. In prostate cancer, improvements in cancer screening modalities have improved the detection of early lesions. The increase in the number of high-risk individuals who do not need to undergo surgery has made chemical blockade of prostate cancer a more urgent need. Since prostate cancer arises from androgens, androgen receptors have become a molecular target for research on chemo-blockers. Many new androgen-eliminating drugs are being or are being considered for clinical studies, such as 5-alpha reductase, a key enzyme in the conversion of testosterone to dihydrotestosterone, which has a high affinity for the androgen receptor. However, there is not yet a well-studied animal model for chemical blockade of prostate cancer, so testing the inhibitory effect of this drug on prostate tumors is still difficult. Also, in the study of chemical blockade of prostate cancer, for androgen receptor models, studies with retinoids or estrogen analogs are an alternative route. A large, phase III randomized study recently conducted by the Proscar Research Organization has been completed with 20,000 individuals adjusted and results are expected within the last five years. V. Molecular biomarkers and intermediate endpoints Biomarkers and intermediate endpoints are a powerful predictor of carcinogenesis for carcinogenesis. Biomarkers can be used as “markers” that the body’s tissues are already diseased. For example, in many epithelial tissues, an early biomarker indicating that the tissue may be cancerous is an increase in DNA aneuploidy of cell differentiation. Other biological markers include genetic and experimental embryological variants such as heterozygous deletions, P53 mutations, increased expression of the epithelial growth factor receptor (EGFP), genomic instability, etc. Biomarkers and intermediate endpoints are very important for chemo-blocking. As predictors of increased risk factors, they help to determine what kind of individuals are likely to develop cancer and suggest what are the high-risk groups. In addition, biomarkers and intermediate endpoints can provide an early discriminator of chemo-blocker effects in a relatively short period of time. If biomarkers and intermediate endpoints can be used as an effective predictor for specific types of cancer, then it will provide an effective and practical tool for scientific research to design more effective and economical chemo-blockers. In conclusion, as the research on oncogenic molecules and cell biology progresses, it will help to identify specific targets for the synthesis of effective new chemo-blocking agents and their application in clinical practice. References: 1. Hong WK, Sporn MB: Recent advances in chemoprevention of cancer. Science, 1997, 278: 1073-1077. 2. 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