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Inhibiting MDR1 Could Cripple Natural Immune Response to Cancers

Jul 21, 2020 10:00:00 AM / by Stacy Matthews Branch, DVM, PhD

3d rendered illustration of the anatomy of a cancer cell_AdobeStock_305639707-1Studies find original efforts to inhibit MDR1 protein function may not be the best course of treatment for cancer patients.

The multidrug-resistant gene (MDR1) codes for p-glycoprotein, was first found in cancer cells and later in normal cells throughout the body. A basic function of MDR1 protein is to pump xenobiotic substances out of the cells as a protective mechanism. This function of MDR1 protein is also found in the blood-brain barrier, protecting the brain from chemicals in the bloodstream. Importantly, many cancer cell types with high levels of MDR1 expression were observed to exhibit resistance to chemotherapeutic drugs

.The discovered role of MDR1 in cancer cell survival suggests that blocking MDR1 may improve the success of cancer chemotherapy. There have been many research efforts to identify a compound that could inhibit MDR1 protein function without adversely affecting normal cells but to no avail. A team of researchers from Scripps Research, Florida and New York University Medical Center found that inhibition of MDR1 may not be a good approach to cancer treatment after all.

The team’s recent research results suggest that MDR1 inhibition may have a deleterious effect on the immune system cells’ ability to mount crucial responses to pathogenic cells. The adverse impact of MDR1 inhibition on cytotoxic T cells and natural killer (NK) cells may be linked to the abundant expression of MDR1 in these cells. Immune cell responses against viruses, bacteria, and cancer cells are impaired by MDR1 protein inhibitors and may explain why these treatments have led to very little clinical success. However, new knowledge can prove valuable in the development of a novel immunotherapy for cancer.

The researchers used MDR1-knockin mice to study the expression of MDR1 in immune cells. MDR1 was found to be constitutively expressed in cytotoxic T cells and NK cells and is essential for immune cell survival by preserving mitochondrial function and preventing T-cell activation-induced oxidative stress. Therefore, MDR1 protein has an important function in cell-mediated immunity, and blocking its function as a means of cancer treatment may be ineffective. The new information regarding MDR1 may help inform the approach to developing immunotherapy involving the tumor-killing capacity of T cells, NK cells, and related components of the immune system.

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Resource: 

Inhibiting Cancer Drug Resistance Gene May Not Be Best Approach. (2020). GEN - Genetic Engineering and Biotechnology News. Retrieved 22 May 2020, from https://www.genengnews.com/news/inhibiting-cancer-drug-resistance-gene-may-not-be-best-approach/

Topics: Cancer, T Cells, NK Cells

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