Future Tumor Hemorrhage Therapy

The rapid proliferation of tumor cells requires a large amount of nutrients, which requires the formation of new blood vessels in the tumor environment to meet this need. Humans discovered that tumor blood vessels expanded and grew rapidly in around a hundred years ago. Later, the dependence between tumor formation and angiogenesis was discovered. Since maintaining tumor vascular integrity is essential for tumor growth, inhibiting tumor blood vessel growth and formation can affect tumor progression. The clinical use of anti-angiogenic drugs together with chemotherapeutic drugs for tumor treatment can give a double hit to the tumor. But there is a contradiction here. The role of anti-angiogenic drugs is to prevent angiogenesis and starve cancer cells. However, chemotherapeutic drugs also enter the tumor through blood vessels. Originally, chemotherapy drugs are not easy to accumulate in tumors. Under normal circumstances, the concentration of drugs in tumors is not as good as that of non-target organs. After the use of anti-angiogenic drugs, the number of tumor blood vessels is greatly reduced, and fewer routes for chemotherapy drugs to enter the tumor. This severely binds the therapeutic effect of the combination.

Figure 1. Tumor Angiogenesis.

Recently, scientists have found a good way to solve this problem. Previous studies have found that under certain pathological conditions, such as in an inflammatory environment, the integrity of blood vessels requires platelets to maintain, otherwise the blood vessels can be damaged. The tumor is precisely the inflammatory environment, which means that platelets are vital to the integrity of the tumor’s blood vessels. Studies have also found that when the thrombocytopenia of tumor mice is reduced, it causes severe intratumoral bleeding and inhibits tumor growth. Therefore, it can be determined that platelets are the main regulators of tumor vascular integrity, and their inhibition selectively makes tumor blood vessels highly permeable and causes a large amount of intratumoral bleeding. Although these results identify platelets as potential targets for anti-tumor therapy, their inhibition cannot be an option for clinical treatment due to their important role in hemostasis. Interesting, the German team of scientists recently found a wonderful way. They find a specific target in tumor blood vessels. By suppressing this target, it can be destroy the tumor blood vessels, greatly increase the permeability, and cause intratumoral bleeding. Moreover, it can also allow chemotherapy drugs to accumulate more in the tumor, greatly improving the therapeutic effect. In this study, scientists using the JAQ1-F (ab) 2 fragment of the antibody to functionally inhibit glycoprotein (GP6) VI on the surface of platelets can rapidly induce tumor hemorrhage and reduce tumor growth, producing effects similar to complete platelet depletion, and does not cause complications of systemic bleeding. These processes can reverse intratumoral hemorrhage and tumor growth arrest by depleting Ly6G+ cells, confirming that they are responsible for inducing intratumoral hemorrhage and necrosis. Furthermore, JAQ1-F (ab) 2-mediated GPVI inhibition increases intratumoral accumulation of co-administered chemotherapeutic agents (eg, docetaxel and paclitaxel), resulting in significant anti-tumor effects. Thus, platelet GPVI has been identified as a key regulator of vascular integrity, particularly in tumor growth, and can serve as a basis for anti-tumor strategies based on interfering platelet function.

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