癌细胞耐受性 z-bo 2020-10-29 368

　　Recently, in a research report titled "An Integrative Gene Expression and Mathematical Flux Balance Analysis Identifies Targetable Redox Vulnerabilities in Melanoma Cells" published in the international magazine Cancer Research, scientists from Vanderbilt University and other institutions have identified through research A special enzyme may be able to maintain the growth of tumor cells during cancer drug therapy. The relevant research results may provide scientists with new ideas and hopes for developing new methods to block the growth of cancer cells.

　　About 10 years ago, many cancer researchers focused on studying mutations in cancer cells and how to turn off these mutations. This focus has paid off in the form of treatment. The new therapies developed by researchers can essentially turn off about half Mutations occur in skin cancer and regulate the expression of genes that regulate tumor cell growth. Unfortunately, this expensive and painstaking treatment also has its limitations. Only half of cancer patients’ tumors disappear within 1 month to 1 year. , And the surviving cancer cells will promote the recurrence of the disease in cancer patients, and this cell will develop a certain resistance to the drug.

　　Researcher Vito Quaranta said, then we began to study at the level of single tumor cells to clarify why some tumors were eliminated during BRAF inhibitor treatment, while other tumors were unharmed; the researchers will study gene expression and metabolomics. The combination of research and data science methods has identified sources of differences that cause some cells to be sensitive to BRAF inhibitors and some cells to be insensitive, in addition to genetic reasons. After analyzing the mechanism of why resistant cells survive and continue to grow in cancer therapy, the researchers analyzed which benchmark metabolic characteristics can promote melanoma cells to become drug-resistant cells. They used The method is different from the genetics-centered view. Researchers hope that cancer therapy can be used as a dynamic change for research, because tumors often change their phenotype.

　　The researchers speculate that the logical place for finding the difference lies in the nutrients and energy received by the cells during and after the BRAF gene is inhibited. Using metabolomics and machine learning methods to classify the cells, the researchers found that drug resistance The energy source of sex cells mainly revolves around redox balance and NOX5. NOX5 is a special enzyme whose level will increase in melanoma that is resistant to therapy. Researcher Quaranta said that the dependence of drug-resistant cells on NOX5 and redox balance is just like when people turn on a generator during a power outage. This enzyme will also produce waste, just like the exhaust gas from a generator. The enhanced antioxidant capacity supported by the cystine transporter SLC7A11 helps to get rid of the cell. Now researchers understand this mechanism, namely the weakness of the enzyme and a refined pathway balancing mechanism.

　　By using the gene expression pattern of a single cell, researchers can use machine learning techniques to understand how the metabolism of different cell types is wired, and can help predict whether specific substances required for the metabolism of drug-resistant cells are higher than those that are sensitive to drugs. Cancer cells; using normal skin cells as a benchmark, researchers can classify cells into drug-resistant cells and sensitive cells, so that drug-resistant cells can be studied more specifically. Researcher McLean said that metabolomics has developed rapidly in the past 10 years, and now researchers can get very influential results by applying it to related research. Now we have determined that NOX5 and redox balance can play a key role in the survival and progression of melanoma, which may change the way the entire cancer research community thinks about how to cure cancer.

　　Since NOX5 does not exist in all tumors, and the redox balance framework in drug-resistant cells may be known in other cancer types, and specific to melanoma-related research, researchers will further study and find A more effective strategy to track NOX5 is to find a way to destroy NOX5 itself, or find a way to inhibit the antioxidant capacity of cells. For other cancer researchers, the results of this article may help them identify The special enzymes of cancer cells that are resistant to other cancer drugs can reveal the weakness of these cancers. In another research report published in the international journal Frontiers in Oncology, researchers analyzed the metabolic composition of drug-resistant cancer cells worldwide, revealing reprogramming that can promote the continued survival of cancer cells during drug therapy treatment During the process, the researchers also speculated that cancer cells that are resistant to the drug may enter a metabolic "idling" state. In the later stage, researchers will continue to conduct in-depth research to reveal other molecular mechanisms of cancer cell resistance to cancer drug therapies, thereby providing new ideas and research foundations for the development of effective therapies.