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Research on new anti-tumor therapy targeting MCL1 protein in melanoma

2021-04-29
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Myeloid cell leukemia-1 (myeloidcellleukemia-1, Mcl-1) is a protein that is highly expressed in cervical cancer, liver cancer, lymphoma, lung cancer and other tumor tissues. It can directly regulate cell differentiation and cell cycle. The occurrence and development are closely related. Recombinant protein expression and protein purification research can lay the foundation for studying the biological function of the protein and drug development. Melanoma is a malignant skin cancer. Recently, scientists from the Centennial Institute reported a new strategy to combat melanoma. Researchers used drugs to inhibit the protein MCL1, as well as from the bromine domain and the extra-external terminus (BET). Family of proteins. Researchers have discovered that these two proteins may effectively kill melanocytes by inducing apoptosis (the process of cell self-destruction that occurs when cells are no longer needed).

In this study, scientists were able to prove that BET and MCL1 inhibitors can effectively reduce the migration and invasiveness of melanoma cells. This is achieved by successfully inhibiting the interaction between two proteins involved in intracellular transport (the process by which molecules pass through the cell membrane of living cells).

BET proteins (BRD2, 3, and 4) are a class of epigenetic regulatory proteins that can bind to acetylated histones. They control the transcription of C-Myc, PIM1, and BCL2 and other growth-promoting and anti-apoptotic target genes. Constructing a protein expression vector and conducting research on the expression of bet recombinant protein in vitro can provide a research basis for studying the function of the protein. The ultimate goal of increasing the expression of the target protein can be achieved by studying the factors and regulation strategies that affect the expression of the recombinant protein. Medicilon has a variety of protein expression systems, including prokaryotic protein expression system, yeast protein expression system, insect cell protein expression system (baculovirus) and mammalian cell protein expression system. It has a variety of fusion technologies and can provide customers with protein expression systems. There are many options for expression and purification.

The expression of BET family is up-regulated in a variety of tumors, and it is related to various biological processes such as cell growth, proliferation and differentiation, apoptosis and necrosis, and then participates in the process of regulating tumor occurrence and development. Phase or phase clinical trials of multiple inhibitors of the BET family are underway. Related research results show that BET inhibitors alone or in combination with existing drugs have clear effects in the treatment of a variety of tumors. Therefore, they are expected to become tumor treatments. New target.

Myeloid leukemia-1 (MCL1) is a newly discovered member of the Bcl-2 family in recent years. It is highly expressed in a variety of tumor tissues and cell lines, and plays an important role in the regulation of apoptosis and the development of tumors. Studies have found that compared with benign nevi, most malignant melanomas have high expression of MCL1 and Bcl-x1. Increased expression of MCL1 and Bcl-x1 first appears in superficial primary melanomas, suggesting that the upregulation of these proteins is malignant In the early manifestation of malignant transformation of melanoma, MCL1 and Bcl-x1 may individually or jointly block the normal cell death pathway, which is related to the pathogenesis and treatment resistance of metastatic malignant melanoma.

Dr. Hsin-YiTseng, the lead author of the study and a researcher in the melanoma oncology and immunology project of the Centennial Research Institute, said, “Due to the high levels of anti-apoptotic proteins or’protector’ proteins found in melanoma cancer cells Therefore, it has proved to be extremely difficult to induce apoptosis. These protective proteins help melanoma cells to survive, grow, and in some cases help resist advanced medical treatments.”

Dr. Hsin-YiTseng said that their research shows that the combined use of BET and MCL1 inhibitors is very effective in killing melanoma. The protective ability of BET and MCL1 proteins declines under the action of drug inhibitors and causes cancer cells to self-destruct.

The senior co-author of this study, Dr. Jwssamy Tiffen, is also a member of the Centennial Institute’s Melanoma Oncology and Immunology Project. She said that the team’s research is of great significance and can provide a potential new treatment strategy for patients with melanoma. Dr. Tiffen said, “About half of melanoma patients do not respond to immunotherapy, and most patients will develop acquired resistance to targeted therapies. Our study tested a large number of human melanoma cell lines and mouse models. We have seen a substantial reduction in melanoma in these cases, which indicates that this research will enter the next stage of development.”

In short, this research is of great significance. In the future fight against advanced melanoma, new treatment strategies can be developed with separate drugs or part of a combined treatment plan.

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