Endostatin is a protein made by human tissues, mostly tumours, but also some normal ones. The first researchers to discover it was a group in 1997. Human endostatin aids in the movement, stickiness, and migration of leukocytes into the blood vessels. Endostatin has been shown to suppress tumour angiogenesis preventing the proliferation and dissemination of cancer, and as such is very much on the tumour therapy radar. Endostatin (an angiogenesis blocker) will normalise the vessels in the tumour, thwart hypoxia, and make tumours more radiation-resistant. Recombinant human endostatin is a new type of selective agent that suppresses angiogenesis, destroys cancer cells and also increases anti-tumour activity of chemotherapy.
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Disease Associated with Deficient Levels of Human Endostatin
A protein produced by endothelial cells called human endostatin contributes to angiogenesis, inflammation and cell proliferation. Human endostatin can cause any number of diseases, mostly those listed below if it is expressed in a way that is not normal:
Cardiovascular Disease
This missing human endostatin induced endothelial dysfunction, promoting atherosclerosis, cardiovascular disease and hypertension.
Inflammatory Diseases
Human endostatin can also control inflammation, and its dysregulated levels are associated with some autoimmune diseases or chronic inflammatory diseases (rheumatoid arthritis, inflammatory bowel disease).
Tumors
In some tumors, EIF might be downregulated, allowing for angiogenesis and subsequent tumor growth and spread.
Recombinant Human Endostatin
Recombinant human endostatin is an endothelial inhibitor for advanced non-small cell lung cancer. It's a natural glycoprotein, highly biologically active and stable. It also prevents tumor endothelial cells from migrating and growing and eventually prevents new blood vessels from forming into the tumor so that it can grow only due to a lack of nutrients and oxygen. Additionally, normal tumor angiogenesis can promote chemotherapy effectiveness, cause endothelial cells to die, and prevent tumor cells from invasively re-invading and spreading.
Anti-angiogenic Mechanism
Endostatin reduces the proliferation and migration of endothelial cells, angiogenesis, and thus tumor blood supply and therefore tumor growth. It also blocks tumor-cell-derived angiogenic factors like VEGF (vascular endothelial growth factor).
Combination Therapy
These most recent research reports suggest that if endostatin is combined with other drugs (eg, chemotherapy, radiotherapy, or immunotherapy), then it might be more effective. This is because combination therapy could hit the tumor from a variety of angles simultaneously and boost the patient's clinical outlook.
The Potential of Targeted Therapy
There are some opportunities for targeted therapy with endostatin, particularly microenvironment control and immunotherapy.
Recombinant Human Endostatin: A Potential Anticancer Agent
The creation of new blood vessels is called angiogenesis (by endothelial cells), and it's a necessary precursor for the formation of a tumour. Blocking angiogenesis is a key component of cancer formation and spread, and it has even been suggested as an anticancer drug. Angiogenesis inhibitors work effectively in some cancer patients, as a single or combined therapy. A variety of cancers are also VM, and we see VM in the creation of capillary-like structures by tumor cells in vitro and the histological appearance of tumor cell-lined vessels in human cancers such as melanomas of the eyes and skin and ovarian cancer. Endostatin, which belongs to the group of endogenous antiangiogenic drug candidates, was already widely used for the treatment of various types of cancers such as:
Advanced Non-small Cell Lung Cancer
The advanced non-small cell lung cancer (NSCLC) is a common lung cancer, which usually undergoes multiple treatments: targeted therapy, chemotherapy, radiotherapy and immunotherapy. Recombinant human endostatin (Apacitinib, Bevacizumab, etc.) is an inhibitor of tumour angiogenesis, and blocks tumour growth and metastasis in certain degrees.
Advanced Esophageal Squamous Cell Carcinoma
The outlook for esophageal squamous cell carcinoma (ESCC) is bad. An angiogenesis inhibitor known as recombinant human endostatin has inhibitory activity against ESCC xenografts. These investigators evaluated recombinant human endostatin and paclitaxel/nedaplatin for recurrent or metastatic advanced ESCC. Activity and safety in patients. Rh-endostatin in combination with paclitaxel/nedaplatin is antitumor and tolerated in recurrent or metastatic advanced ESCC. It would require randomized controlled trials to verify this regimen.
Triple-negative Breast Cancer
An aggressive type of breast cancer, triple-negative breast cancer (TNBC), occurs mainly by way of metastases. Angiogenesis promotes TNBC metastasis. Many TNBCs create vessels clogged by tumor cells rather than endothelial cells. TNBC expresses a lot of the epidermal growth factor receptor (EGFR) , and anti-EGFR antibodies are not very effective. We constructed an anti-EGFR antibody-endostatin fusion protein EGFR-E-P125A, which acts as a delivery system for mutant endostatin huEndo-P125A (E-P125A) to EGFR-positive tumors, and evaluated its contribution to angiogenesis, TNBC VM and motility in vitro and growth and metastasis in two independent human TNBC xenograft models.
Conclusion
Recombinant human endostatin is one biological drug that has become very popular in the treatment of tumors. Its main role is to prevent angiogenesis, which prevents tumor development and spread. The first process in the formation of tumors is called angiogenesis. If tumor cells are encouraged to form new blood vessels surrounding the tumor, they can take in more oxygen and nutrients and grow fast. Now that the tumor microenvironment has been fully mapped, the research on recombinant human endostatin continues to build. In the future, maybe even more individualized treatments for specific tumor types.
The use of recombinant human endostatin in cancer therapy holds promise, though the effects and safety on the long-term side still require testing. Totodatly, research in conjunction with other treatments will also play a role going forward.
References
- Shin, S.; et al. Inhibition of vasculogenic mimicry and angiogenesis by an anti-EGFR IgG1-human endostatin-P125A fusion protein reduces triple negative breast cancer metastases. Cells. 2021, 10(11): 2904.
- Wang, Z.; et al. Recombinant human endostatin plus paclitaxel/nedaplatin for recurrent or metastatic advanced esophageal squamous cell carcinoma: a prospective, single-arm, open-label, phase II study. Investigational New Drugs. 2021, 39: 516-523.
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