At the latter stage of cancer, chemotherapy is often the only available therapeutic approach. Yet chemotherapy is not effective against many solid tumors. Many studies have shown that the lack of selectivity of chemotherapy drugs dramatically increases the risk of the development of cellular resistance by tumors cells. A fraction of chemotherapy agents can promote immunogenic cell death and consequently alter the tumor microenvironment in terms of immune cells and inflammation. In addition, chemotherapy may affect the acquisition of drug-resistant clones, or survival of cancer stem cells that may further promote tumorigenesis. To reduce adverse effects and to increase treatment efficacy, scientists at Creative Biolabs have been working on finding ways to specifically target solid tumors for many years. Recently, we launch the SE-Enzym™ tumor microenvironment (TME) targeting chemotherapy technology platform for the development of chemotherapy therapy with high selectivity, boosting efficacy while reducing adverse effects.
Genetic/epigenetic changes in the tumor cells and the rearrangement of the components of the TME through mutual and dynamic crosstalk influence the process of tumor formation and progression. TME is comprised of tumor cells, tumor stromal cells including immune cells, stromal fibroblasts and endothelial cells, and the non-cellular components of extracellular matrix including collagen, fibronectin, hyaluronan, among others. Tumor cells, the heart of TME, control the function of cellular and non-cellular components through complex signaling networks to use the non-malignant cells to work for their benefit. In addition, the non-malignant cells in the TME are known to promote tumorigenesis in all phases of cancer development and metastasis. Chemotherapy can directly kill or damage cancer cells, and chemotherapeutic drugs can also remodel the TME which promotes tumor regrowth and drug resistance.
Fig.1 Tumor microenvironment at a glance. (Baghban, 2020)
The features of SE-Enzym™ chemotherapy are as follows, which can achieve a much higher selective treatment, reduce adverse effects and increase the quality of life:
An ideal prodrug, which increases the bioavailability of an antitumor drug, is designed to slowly release. Following activation, the drug is transported via the bloodstream to the tumor site where it can execute its mode of action. Prodrugs are activated by enzymes with high catalytic efficiencies, leading to rapid activation of the prodrug. Moreover, due to the reactivity of most antitumor drugs, the limitation of prodrugs activated by enzymes with low catalytic efficiencies is that frequently nontumor tissues are also affected and the metabolism of these prodrugs by competing for enzymes into inactive metabolites.
Multiple enzymes have been employed to activate prodrugs of antitumor agents. All of these enzymes belong to four International Union of Pure and Applied Chemistry classes. Enzymes from class 1 are the oxidoreductases, such as aldehyde oxidase, amino acid oxidase; Enzymes from class 2 represent the transferases, such as thymidylate synthase, thymidine phosphorylase; Enzymes from class 3 are hydrolases, such as carboxylesterase, alkaline phosphatase; and Enzymes from class 4 represent the lyases, such as cysteine conjugate β-Lyase.
For more details about our SE-Enzym™ TME targeting chemotherapy technology platform, please do not hesitate to contact us.
References
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